基本情報

所属

• 先端生命科学研究院　先端融合科学研究部門　化学生物学分野

職名

• 教授

学位

• 理学博士（北海道大学）
• 理学修士（北海道大学）

ホームページURL

http://altair.sci.hokudai.ac.jp/infchb/
http://www.lfsci.hokudai.ac.jp/labs/infchb/

科研費研究者番号

• 40210207

J-Global ID

• 200901036377662744

研究キーワード

• 不妊治療   アルツハイマー病   阻害剤   複合糖質・脂質   化学生物学   赤外円二色スペクトル   キラリティー   

研究分野

• ナノテク・材料 / 生体化学
• ナノテク・材料 / ケミカルバイオロジー

担当教育組織

•  学士課程　理学部
•  修士課程　生命科学院
•  博士課程　生命科学院

職歴

• 2024年04月 - 現在 内閣府 科学技術・イノベーション推進事務局 上席科学技術政策フェロー
• 2024年04月 - 現在 北海道大学 副理事
• 2023年04月 - 現在 北海道大学 大学院先端生命科学研究院 副研究院長
• 2016年04月 - 現在 北海道大学 大学院先端生命科学研究院 次世代物質生命科学研究センター長
• 2010年04月 - 現在 北海道大学 大学院先端生命科学研究院（化学生物学分野） 教授
• 2023年04月 - 2024年03月 北海道大学 総長補佐
• 2019年04月 - 2023年03月 北海道大学 大学院先端生命科学研究院 研究院長
• 2019年01月 - 2023年03月 理化学研究所 客員主管研究員
• 2013年04月 - 2019年03月 北海道大学 先端生命科学研究院 副研究院長
• 2013年04月 - 2016年03月 北海道大学 先端生命科学研究院 次世代ポストゲノム研究センター長
• 2006年04月 - 2010年03月 北海道大学 先端生命科学研究院（先端生体制御科学分野） 准教授
• 2001年07月 - 2006年03月 北海道大学 理学研究科（生物科学専攻生体高分子設計学講座） 助教授
• 1996年07月 - 2001年06月 東北大学 （反応化学研究所生体反応制御分野） 助手
• 1995年01月 - 1996年06月 米国コロンビア大学 博士研究員
• 1994年03月 - 1995年01月 文部省在外研究員（米国コロンビア大学） 博士研究員
• 1988年04月 - 1994年03月 北海道大学 （理学部化学科環境化学講座） 助手

学歴

• 1986年04月 - 1988年03月   北海道大学   理学研究科   化学専攻（博士後期課程）
• 1984年04月 - 1986年03月   北海道大学   理学研究科   化学専攻（博士前期課程）
• 1980年04月 - 1984年03月   北海道大学   理学部   化学科

所属学協会

• 日本脂質生化学会   日本化学会   アメリカ化学会   高分子学会   有機合成化学協会   セラミド研究会   日本糖質学会   フルオラス科学研究会   日本油化学会   日本ケミカルバイオロジー学会   

研究活動情報

論文

• Isolation and Structure Determination of cis-OPDA-α-Monoglyceride from Arabidopsis thaliana.

  Shotaro Hirota, Yusuke Ito, Shiro Inoue, Naoki Kitaoka, Tohru Taniguchi, Kenji Monde, Kosaku Takahashi, Hideyuki Matsuura

  Journal of natural products 2024年04月24日 

  cis-12-oxo-Phytodieneoic acid-α-monoglyceride (1) was isolated from Arabidopsis thaliana. The chemical structure of 1 was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the cis-OPDA moiety in 1 was determined by comparison of 1H NMR spectra and ECD measurements. With respect to the absolute configuration of the β-position of the glycerol backbone, the 2:3 ratio of (S) to (R) was determined by making ester-bonded derivatives with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride and comparing 1H NMR spectra. Wounding stress did not increase endogenous levels of 1, and it was revealed 1 had an inhibitory effect of A. thaliana post germination growth. Notably, the endogenous amount of 1 was higher than the amounts of (+)-7-iso-jasmonic acid and (+)-cis-OPDA in intact plants. 1 also showed antimicrobial activity against Gram-positive bacteria, but jasmonic acid did not. It was also found that α-linolenic acid-α-monoglyceride was converted into 1 in the A. thaliana plant, which implied α-linolenic acid-α-monoglyceride was a biosynthetic intermediate of 1.
• Biocompatible and Water-Soluble Shortwave-Infrared (SWIR)-Emitting Cyanine-Based Fluorescent Probes for In Vivo Multiplexed Molecular Imaging

  Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde, Setsuko Tsuboi, Aravind K. Swamy, Takashi Jin

  ACS Applied Materials Interfaces 2024年04月 [査読有り]
  
• Racemization of the substrate and product by serine palmitoyltransferase from Sphingobacterium multivorum yields two enantiomers of the product from d-serine

  Hiroko Ikushiro, Takumi Honda, Yuta Murai, Taiki Murakami, Aya Takahashi, Taiki Sawai, Haruna Goto, Shin-ichi Ikushiro, Ikuko Miyahara, Yoshio Hirabayashi, Nobuo Kamiya, Kenji Monde, Takato Yano

  Journal of Biological Chemistry 300 3 105728 - 105728 2024年03月 [査読有り]
  
• Photoinduced dual bond rotation of a nitrogen-containing system realized by chalcogen substitution

  Shotaro Nagami, Rintaro Kaguchi, Taichi Akahane, Yu Harabuchi, Tohru Taniguchi, Kenji Monde, Satoshi Maeda, Satoshi Ichikawa, Akira Katsuyama

  Nature Chemistry 2024年02月28日 [査読有り]
  
• Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality

  Sajeer Koolath, Yuta Murai, Tomoya Suzuki, Mahadeva M. M. Swamy, Seigo Usuki, Kenji Monde

  ACS Medicinal Chemistry Letters 14 9 1237 - 1241 2023年08月 [査読有り]
  
• Structural insights into the substrate recognition of serine palmitoyltransferase from Sphingobacterium multivorum

  Hiroko Ikushiro, Taiki Murakami, Aya Takahashi, Asuka Katayama, Taiki Sawai, Haruna Goto, Sajeer Koolath, Yuta Murai, Kenji Monde, Ikuko Miyahara, Nobuo Kamiya, Takato Yano

  Journal of Biological Chemistry 299 5 104684 - 104684 2023年05月 [査読有り]
  
• Stereochemistry‐activity relationship of ceramide‐induced exosome production to clear amyloid‐β in Alzheimer's disease

  Mariam Abdelrasoul, Kohei Yuyama, Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde

  Chirality 35 9 577 - 585 2023年04月 [査読有り]
   

  Abstract Stereochemistry has a substantial impact on the biological activity of various drugs. We investigated the role of stereochemistry of ceramides in inducing the production of exosomes, a type of extracellular vesicle, from neuronal cells, with a potential benefit in improving the clearance of amyloid‐β (Aβ), a causal agent of Alzheimer's disease. A stereochemical library of diverse ceramides with different tail lengths was synthesized with the purpose of varying stereochemistry (D‐erythro: DE, D‐threo: DT, L‐erythro: LE, L‐threo: LT) and hydrophobic tail length (C6, C16, C18, C24). The exosome levels were quantified using TIM4‐based exosome enzyme‐linked immunosorbent assay after concentrating the conditioned medium using centrifugal filter devices. The results revealed a pivotal role of stereochemistry in determining the biological activity of ceramide stereoisomers, with the superiority of those based on DE and DT stereochemistry with C16 and C18 tails, which demonstrated significantly higher exosome production, without a significant change in the particle size of the released exosomes. In transwell experiments with Aβ‐expressed neuronal and microglial cells, DE‐ and DT‐ceramides with C16 and C18 tails significantly decreased extracellular Aβ levels. The results reported here are promising in the design of non‐classic therapies for the treatment of Alzheimer's disease.
• Total Synthesis, Absolute Configuration, and Phytotoxic Activity of Foeniculoxin

  Akane Yamagishi, Yuki Egoshi, Makoto T. Fujiwara, Noriyuki Suzuki, Tohru Taniguchi, Ryuuichi D. Itoh, Yumiko Suzuki, Yoshiro Masuyama, Kenji Monde, Toyonobu Usuki

  Chemistry – A European Journal 2022年11月 [査読有り]
  
• Stereoselective Construction of Fluorinated Quaternary Stereogenic Centers via an Organocatalytic Asymmetric exo-Selective Diels–Alder Reaction in the Presence of Water

  Bojan P. Bondzić, Konstantinos Daskalakis, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi

  Organic Letters 24 40 7455 - 7460 2022年10月 [査読有り]
  
• Immuno-digital invasive cleavage assay for analyzing Alzheimer's amyloid ß-bound extracellular vesicles.

  Kohei Yuyama, Hui Sun, Yasuyuki Igarashi, Kenji Monde, Takumi Hirase, Masato Nakayama, Yoichi Makino

  Alzheimer's research & therapy 14 1 140 - 140 2022年10月 [査読有り]
   

  BACKGROUND: The protracted preclinical stage of Alzheimer's disease (AD) provides the opportunity for early intervention to prevent the disease; however, the lack of minimally invasive and easily detectable biomarkers and their measurement technologies remain unresolved. Extracellular vesicles (EVs) are nanosized membrane vesicles released from a variety of cells and play important roles in cell-cell communication. Neuron-derived and ganglioside-enriched EVs capture amyloid-ß protein, a major AD agent, and transport it into glial cells for degradation; this suggests that EVs influence Aß accumulation in the brain. EV heterogeneity, however, requires the use of a highly sensitive technique for measuring specific EVs in biofluid. In this study, immuno-digital invasive cleavage assay (idICA) was developed for quantitating target-intact EVs. METHODS: EVs were captured onto ganglioside GM1-specific cholera toxin B subunit (CTB)-conjugated magnetic beads and detected with a DNA oligonucleotide-labeled Aß antibody. Fluorescence signals for individual EVs were then counted using an invasive cleavage assay (ICA). This idICA examines the Aß-bound and GM1-containing EVs isolated from the culture supernatant of human APP-overexpressing N2a (APP-N2a) cells and APP transgenic mice sera. RESULTS: The idICA quantitatively detected Aß-bound and GM1-containing EVs isolated from culture supernatants of APP-N2a cells and sera of AD model mice. The idICA levels of Aß-associated EVs in blood gradually increased from 3- to 12-month-old mice, corresponding to the progression of Aß accumulations in the brain of AD model mice. CONCLUSIONS: The present findings suggest that peripheral EVs harboring Aß and GM1 reflect Aß burden in mice. The idICA is a valuable tool for easy quantitative detection of EVs as an accessible biomarker for preclinical AD diagnosis.
• Evaluation of Plant Ceramide Species-Induced Exosome Release from Neuronal Cells and Exosome Loading Using Deuterium Chemistry

  Yuta Murai, Takumi Honda, Kohei Yuyama, Daisuke Mikami, Koichi Eguchi, Yuichi Ukawa, Seigo Usuki, Yasuyuki Igarashi, Kenji Monde

  International Journal of Molecular Sciences 23 18 10751 - 10751 2022年09月 [査読有り]
   

  The extracellular accumulation of aggregated amyloid-β (Aβ) in the brain leads to the early pathology of Alzheimer’s disease (AD). The administration of exogenous plant-type ceramides into AD model mice can promote the release of neuronal exosomes, a subtype of extracellular vesicles, that can mediate Aβ clearance. In vitro studies showed that the length of fatty acids in mammalian-type ceramides is crucial for promoting neuronal exosome release. Therefore, investigating the structures of plant ceramides is important for evaluating the potential in releasing exosomes to remove Aβ. In this study, we assessed plant ceramide species with D-erythro-(4E,8Z)-sphingadienine and D-erythro-(8Z)-phytosphingenine as sphingoid bases that differ from mammalian-type species. Some plant ceramides were more effective than mammalian ceramides at stimulating exosome release. In addition, using deuterium chemistry-based lipidomics, most exogenous plant ceramides were confirmed to be derived from exosomes. These results suggest that the ceramide-dependent upregulation of exosome release may promote the release of exogenous ceramides from cells, and plant ceramides with long-chain fatty acids can effectively release neuronal exosomes and prevent AD pathology.
• Penta-deuterium-labeled 4E, 8Z-sphingadienine for rapid analysis in sphingolipidomics study

  Yuta Murai, Kohei Yuyama, Daisuke Mikami, Yasuyuki Igarashi, Kenji Monde

  Chemistry and Physics of Lipids 245 105202 - 105202 2022年07月 [査読有り]
   

  The use of deuterium-incorporated bioactive compounds is an efficient method for tracing their metabolic fate and for quantitative analysis by mass spectrometry without complicated HPLC separation even if their amounts are extremely small. Plant sphingolipids and their metabolites, which have C4, 8-olefins on a common backbone as a sphingoid base, show unique and fascinating bioactivities compared to those of sphingolipids in mammals. However, the functional and metabolic mechanisms of exogenous plant sphingolipids have not been elucidated due to the difficulty in distinguishing exogenous sphingolipids from endogenous sphingolipids having the same polarity and same molecular weight by mass spectrometric analysis. Their roles might be elucidated by the use of deuterated probes with original biological and physicochemical properties. In this study, we designed (2S,3R,4E,8Z)-2-aminooctadeca-4,8-diene-17,17,18,18,18-d5-1,3-diol (penta-deuterium-labeled 4E, 8Z-sphingadienine) as a tracer for exogenous metabolic studies. In addition, the sphingadienine was confirmed to be metabolized in HEK293 cells and showed distinct peaks in mass spectrometric analysis.
• Control of Reactions of Pyruvates by Catalysts: Direct Enantioselective Mannich Reactions of Pyruvates Catalyzed by Amine-based Catalyst Systems

  Santanu Mondal, Ravindra D. Aher, Venkati Bethi, Yu-Ju Lin, Tohru Taniguchi, Kenji Monde, Fujie Tanaka

  Organic Letters 24 9 1853 - 1858 2022年03月 [査読有り]
  
• Evaluation of chiral N , N ‐dimethyl‐sphingosine for the interaction between nerve growth factor and tropomyosin receptor kinase A

  Yuta Murai, Akihiro Sekiguchi, Taeko Hirakawa, Seigo Usuki, Yasuyuki Igarashi, Kenji Monde

  Chirality 34 807 - 812 2022年02月 [査読有り]
  
• A near-infrared fluorescent long-chain fatty acid toward optical imaging of cardiac metabolism in living mice

  Mahadeva M. M. Swamy, Mohamad Zarif Mohd Zubir, Mutmainah, Setsuko Tsuboi, Yuta Murai, Kenji Monde, Ken-ichi Hirano, Takashi Jin

  The Analyst 147 19 4206 - 4212 2022年 [査読有り]
   

  A near infrared fluorescence labelled long-chain fatty acid (FFA), Alexa680-BMPP (BMPP: 15-(4-(3-aminopropyl)phenyl)-3-methyl pentadecanoic acid), was synthesized as a fluorescent probe toward optical imaging of cardiac metabolism.
• Shortwave-infrared (SWIR) emitting annexin V for high-contrast fluorescence molecular imaging of tumor apoptosis in living mice

  Mahadeva M. M. Swamy, Setsuko Tsuboi, Yuta Murai, Kenji Monde, Takashi Jin

  RSC Advances 12 30 19632 - 19639 2022年 [査読有り]
   

  The labelling of annexin V with indocyanine green (ICG) and π-conjugation extended ICG (ICG-C11) resulted in SWIR emitting probes that enable high-contrast molecular imaging of tumor apoptosis in living mice.
• Stereostructural analysis of flexible oxidized fatty acids by VCD spectroscopy

  Tohru Taniguchi, Naka Ida, Takuya Kitahara, Davidson Obinna Agbo, Kenji Monde

  Chemical Communications 58 41 6116 - 6119 2022年 [査読有り]
   

  Using VCD spectroscopy to elucidate absolute configuration and conformational preferences of hydroxy fatty acids, lipid epoxides, and lipid hydroperoxides.
• Deuterium labelling to extract local stereochemical information by VCD spectroscopy in the C–D stretching region: a case study of sugars

  Mohamad Zarif Mohd Zubir, Nurul Fajry Maulida, Yoshihiro Abe, Yuta Nakamura, Mariam Abdelrasoul, Tohru Taniguchi, Kenji Monde

  Organic & Biomolecular Chemistry 20 5 1067 - 1072 2022年 [査読有り]
   

  Methoxy-d₃ group installed at the C-1 position of a series of epimeric pairs of sugars generated mirror-image VCD patterns in the 2300–1900 cm⁻¹ region depending on the C-1 stereochemistry irrespective of the configurations at other positions.
• Synthesis of Bicyclo[2.2.2]octanes with a Quaternary Bridgehead Carbon by Diphenylprolinol Silyl Ether‐mediated Domino Reaction

  Nariyoshi Umekubo, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi

  Asian Journal of Organic Chemistry 10 12 3261 - 3265 2021年12月 [査読有り]
  
• Exploration of chromophores for a VCD couplet in a spectrally transparent infrared region for biomolecules

  Tohru Taniguchi, Mohamad Zarif Mohd Zubir, Nobuyuki Harada, Kenji Monde

  Physical Chemistry Chemical Physics 23 48 27525 - 27532 2021年11月 [査読有り]
   

  Introduction of chromophores in the 2300–2000 cm⁻¹ region such as nitrile and azido groups yields strong VCD signals whose shapes are indicative of molecular structures, as studied by experimental work and theoretical calculations.
• Enantiodivergent One‐Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst‐Mediated Enantioselective Domino Reaction and Central‐to‐Axial Chirality Conversion

  Seitaro Koshino, Tohru Taniguchi, Kenji Monde, Eunsang Kwon, Yujiro Hayashi

  Chemistry – A European Journal 27 63 15786 - 15794 2021年11月 [査読有り]
  
• Shortwave-Infrared Fluorescent Molecular Imaging Probes Based on π-Conjugation Extended Indocyanine Green

  Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde, Setsuko Tsuboi, Takashi Jin

  Bioconjugate Chemistry 32 8 1541 - 1547 2021年08月18日 [査読有り]
   

  Recently, shortwave-infrared (SWIR) fluorescence imaging for the optical diagnostics of diseases has attracted much attention as a new noninvasive imaging modality. For this application, the development of SWIR molecular imaging probes with high biocompatibility is crucial. Although many types of biocompatible SWIR fluorescent probes based on organic dyes have been reported, there are no SWIR-emitting molecular imaging probes that can be used for the detection of specific biomolecules in vivo. To apply SWIR-emitting molecular imaging probes to biomedical fields, we developed a biocompatible SWIR fluorescent dye based on π-conjugation extended indocyanine green (ICG), where ICG is the only approved near-infrared dye by the US Food and Drug Administration (FDA) for use in the clinic. Using the π-conjugation extended ICG, we prepared SWIR molecular imaging probes that can be used for in vivo tumor imaging. Herein, we demonstrate noninvasive SWIR fluorescence imaging of human epidermal growth factor receptor 2 (HER2)-positive and epidermal growth factor receptor (EGFR)-positive breast tumors using π-conjugation extended ICG and monoclonal antibody conjugates. The presented π-conjugation extended ICG analog probes will be a breakthrough to apply SWIR fluorescence imaging in biomedical fields.
• こんにゃく由来グルコシルセラミド摂取による脳内アミロイドβ蓄積に対する抑制効果の探索的試験－プラセボ対照ランダム化二重盲検並行群間比較試験－

  江口 晃一, 向井 克之, 湯山 耕平, 栗本 成敬, 田中 藍子, 勝山(鏡) 豊代, 西平 順, 門出 健次, 五十嵐 靖之

  薬理と治療 49 8 1225 - 1239 2021年 [査読有り]
  
• Daurichromenic Acid from the Chinese Traditional Medicinal Plant Rhododendron dauricum Inhibits Sphingomyelin Synthase and Aβ Aggregation

  Hadya Virupaksha Deepak, Mahadeva M. M. Swamy, Yuta Murai, Yoshiko Suga, Masaki Anetai, Takuro Yo, Masahiro Kuragano, Koji Uwai, Kiyotaka Tokuraku, Kenji Monde

  Molecules 25 18 4077 - 4088 2020年09月 [査読有り][通常論文]
   

  Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC50 of 4 µM. The structure–activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA.
• Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step

  Seitaro Koshino, Akira Takikawa, Keiichi Ishida, Tohru Taniguchi, Kenji Monde, Eunsang Kwon, Shigenobu Umemiya, Yujiro Hayashi

  Chem. Eur. J. 26 20 4524 - 4530 2020年04月06日 [査読有り][通常論文]
  
• Effect of circularly polarized light on germination, hypocotyl elongation and biomass production of arabidopsis and lettuce: Involvement of phytochrome B

  Enkhsukh Lkhamkhuu, Kazunori Zikihara, Hitomi Katsura, Satoru Tokutomi, Takafumi Hosokawa, Yoshihisa Usami, Mitsuyoshi Ichihashi, Junji Yamaguchi, Kenji Monde

  Plant Biotechnology 37 1 57 - 67 2020年03月25日 [査読有り][通常論文]
   

  Circular dichroism (CD), defined as the differential absorption of left- and right-handed circularly polarized light (CPL), is a useful spectroscopic technique for structural studies of biological systems composed of chiral molecules. The present study evaluated the effects of CPL on germination, hypocotyl elongation and biomass production of Arabidopsis and lettuce. Higher germination rates were observed when Arabidopsis and lettuce seedlings were irradiated with red right-handed CPL (R-CPL) than with red left-handed CPL (L-CPL). Hypocotyl elongation was effectively inhibited when Arabidopsis and lettuce seedlings were irradiated with red R-CPL than with red L-CPL. This difference was not observed when a phytochrome B (phyB) deficient mutant of Arabidopsis was irradiated, suggesting that inhibition of elongation by red R-CPL was mediated by phyB. White R-CPL induced greater biomass production by adult Arabidopsis plants, as determined by their fresh shoot weight, than white L-CPL. To determine the molecular basis of these CPL effects, CD spectra and the effect of CPL on the photoreaction of a sensory module of Arabidopsis phyB were measured. The red light-absorbing form of phyB showed a negative CD in the red light-absorbing region, consistent with the results of germination, inhibition of hypocotyl elongation and biomass production. L-CPL and R-CPL, however, did not differ in their ability to induce the interconversion of the red light-absorbing and far-red light-absorbing forms of phyB. These findings suggest that these CPL effects involve phyB, along with other photoreceptors and the photosynthetic process.
• Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase.

  Sajeer Koolath, Yuta Murai, Yoshiko Suga, Kenji Monde

  Chirality 32 3 308 - 313 2020年03月 [査読有り][通常論文]
   

  Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules.
• Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain.

  Seigo Usuki, Yoshiaki Yasutake, Noriko Tamura, Tomohiro Tamura, Kunikazu Tanji, Takashi Saitoh, Yuta Murai, Daisuke Mikami, Kohei Yuyama, Kenji Monde, Katsuyuki Mukai, Yasuyuki Igarashi

  Cells 9 2 2020年02月24日 [査読有り][通常論文]
   

  Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and a-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand-receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.
• Design and Synthesis of Ligand‐Tag Exchangeable Photoaffinity Probe Utilizing Nosyl Chemistry

  Saaidin S. A., Murai, Y., Ishikawa, T., Monde, K.

  Eur. J. Org. Chem. 2019 46 7563 - 7567 2019年12月 [査読有り][通常論文]
  
• Malabaricone C as Natural Sphingomyelin Synthase Inhibitor against Diet-Induced Obesity and Its Lipid Metabolism in Mice.

  Muhamad Aqmal Othman, Kohei Yuyama, Yuta Murai, Yasuyuki Igarashi, Daisuke Mikami, Yasodha Sivasothy, Khalijah Awang, Kenji Monde

  ACS medicinal chemistry letters 10 8 1154 - 1158 2019年08月08日 [査読有り][通常論文]
   

  The interaction between natural occurring inhibitors and targeted membrane proteins could be an alternative medicinal strategy for the treatment of metabolic syndrome, notably, obesity. In this study, we identified malabaricones A-C and E (1-4) isolated from the fruits of Myristica cinnamomea King as natural inhibitors for sphingomyelin synthase (SMS), a membrane protein responsible for sphingolipid biosynthesis. Having the most promising inhibition, oral administration of compound 3 exhibited multiple efficacies in reducing weight gain, improving glucose tolerance, and reducing hepatic steatosis in high fat diet-induced obesity mice models. Liver lipid analysis revealed a crucial link between the SMS activities of compound 3 and its lipid metabolism in vitro and in vivo. The nontoxic nature of compound 3 makes it a suitable candidate in search of drugs which can be employed in the treatment and prevention of obesity.
• First enantioselective synthesis of salinipostin A, a marine cyclic enol-phosphotriester isolated from Salinispora sp

  Hironori Okamura, Takanobu Fujioka, Naoki Mori, Tohru Taniguchi, Kenji Monde, Hidenori Watanabe, Hirosato Takikawa

  Tetrahedron Letters 60 32 150917 - 150917 2019年08月 [査読有り][通常論文]
  
• An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes.

  Rina Sasaki, Reina Tainaka, Yuichi Ando, Yurika Hashi, Hadya V Deepak, Yoshiko Suga, Yuta Murai, Masaki Anetai, Kenji Monde, Kiminori Ohta, Ikuko Ito, Haruhisa Kikuchi, Yoshiteru Oshima, Yasuyuki Endo, Hitomi Nakao, Masafumi Sakono, Koji Uwai, Kiyotaka Tokuraku

  Sci. Rep. 9 1 2587 - 2587 2019年02月 [査読有り][通常論文]
   

  Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer's disease, Parkinson's disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range of compounds and aggregation-prone polypeptides.
• Determination of the Absolute Configurations and the Sensory Properties of the Enantiomers of a Homologous Series (C6–C10) of 2-Mercapto-4-alkanones

  Kiske, C, Riegel, A, Hopf, R, Kvindt, A, Poplacean, I, Taniguchi, T, Swamy, M, Monde, K, Eisenreich, W, Engel, K

  J. Agric. Food Chem. 67 4 1187 - 1196 2019年01月 [査読有り][通常論文]
  
• Structure-inspired design of a sphingolipid mimic sphingosine-1-phosphate receptor agonist from a naturally occurring sphingomyelin synthase inhibitor.

  Mahadeva M M Swamy, Yuta Murai, Yusuke Ohno, Keisuke Jojima, Akio Kihara, Susumu Mitsutake, Yasuyuki Igarashi, Jian Yu, Min Yao, Yoshiko Suga, Masaki Anetai, Kenji Monde

  Chemical communications (Cambridge, England) 54 90 12758 - 12761 2018年11月08日 [査読有り][通常論文]
   

  Ginkgolic acid obtained as a sphingomyelin synthase inhibitor from a plant extract library inspired the concept of sphingolipid mimics. Ginkgolic acid-derived N-acyl anilines and ginkgolic acid 2-phosphate (GA2P) respectively mimic ceramide and sphingosine 1-phosphate (S1P) in structure and function. The GA2P-induced phosphorylation of ERK and internalization of S1P receptor 1 (S1P1) indicated potent agonist activity. Docking studies revealed that GA2P adopts a similar binding conformation to the bound ligand ML5, which is a strong antagonist of S1P1.
• Preparation of Carbodiimides with One-Handed Axial Chirality

  Taniguchi, T, Suzuki, T, Satoh, H, Shichibu, Y, Konishi, K, Monde, K

  J. Am. Chem. Soc. 140 46 15577 - 15581 2018年11月 [査読有り][通常論文]
  
• Synthesis and Photochemical Properties of Axially Chiral Bis(dinaphthofuran)

  Katakami, C, Kamo, S, Torii, A, Hara, N, Imai, Y, Taniguchi, T, Monde, K, Okabayashi, Y, Hosokai, T, Kuramochi, K, Tsubaki, K

  J. Org. Chem. 83 23 14610 - 14616 2018年10月 [査読有り][通常論文]
   

  Both enantiomers of axially chiral bis-(dinaphthofuran) were prepared in only two steps from 1'-hydroxy-4'-methoxy-2,2'-binaphthalenyl-1,4-dione, followed by optical resolution via high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP). The absolute configurations were determined by comparison of experimental and calculated vibrational circular dichroism (VCD) spectra. Synthetic bis(dinaphthofuran) exhibited a broad and unstructured emission derived from an intramolecular excimer in both solution and solid state. The methylene bridge brings both chromophores close to each other and induces significant changes in the photophysical behavior. Chiral bis(dinaphthofuran) displayed a bathochromic shift in emission, as compared to the racemic mixture in the solid state. Furthermore, the compounds showed high circularly polarized luminescence (CPL) with a dissymmetry factor (g(lum)) of 10(-3) at 405 nm upon excitation at 265 nm in a methanol solution. This compound serves as a model for the design and synthesis of organic materials having CPL activity.
• Palladium-Catalyzed Asymmetric C(sp³)-H Allylation of 2-Alkylpyridines

  Murakami R, Sano K, Iwai T, Taniguchi T, Monde K, Sawamura M

  Angew. Chem., Int. Ed. 57 30 9465 - 9469 2018年07月 [査読有り][通常論文]
   

  The palladium-catalyzed asymmetric side-chain C(alpha)-allylation of 2-alkylpyridines, without using an external base, was developed. The high linear selectivities and enantioselectivities were achieved using new chiral diamidophosphite monodentate ligands. Given that the reaction conditions do not require an external base, this catalyst system enabled chemoselective C(alpha)-allylation of 2-alkylpyridines containing alpha-carbonyl C-H bonds, which are more acidic than alpha-pyridyl C-H bonds.
• Enantio- and Diastereoselective Synthesis of Latanoprost using an Organocatalyst

  Genki Kawauchi, Shigenobu Umemiya, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi

  Chemistry - A European Journal 24 33 8409 - 8414 2018年06月12日 [査読有り][通常論文]
   

  An enantioselective total synthesis of latanoprost was achieved. Its chiral cyclopentane core structure was constructed through an organocatalyst-mediated [3+2]-cycloaddition reaction, and chirality in the ω-side chain was generated by prolinate-anion-mediated α-aminoxylation of an aldehyde. Highly diastereoselective domino acetalization and an oxy-Michael reaction were key steps for the generation of C9 chirality.
• Modifying oligoalanine conformation by replacement of amide to ester linkage

  Takahiro Hongen, Tohru Taniguchi, Kenji Monde

  Chirality 30 4 396 - 401 2018年04月01日 [査読有り][通常論文]
   

  Oligo(lactic acid) is an ester-analogue of short oligoalanine sequence and adopts a rigid left-handed helical structure. In this study, oligo(lactic acid) was incorporated into oligoalanine sequences and their conformations were studied by vibrational circular dichroism and electronic circular dichroism spectroscopy. The results suggested that oligo(lactic acid) moiety in these sequences maintains a left-handed helix and increases the conformational propensity of the oligoalanine moiety to form a left-handed polyproline type II-like helix. The importance of the chirality of oligo(lactic acid) moiety for the oligoalanine conformation was also studied. The results obtained in this study should be useful in developing ester-containing oligopeptides that function better than normal peptides.
• Stereochemistry (and Conformation) of Nucleosides and Their Synthetic Precursors by Vibrational Circular Dichroism

  Taniguchi, T, Nakano, K, Monde, K

  Current Protocols in Nucleic Acid Chemistry 72 1 7.29.1 - 7.29.9 2018年03月 [査読有り][通常論文]
  
• Facile Chemoselective Strategy toward Capturing Sphingoid Bases by a Unique Glutaraldehyde-Functionalized Resin.

  Siddabasave Gowda B Gowda, Atsufumi Nakahashi, Keiko Yamane, Saori Nakahashi, Yuta Murai, Ananda Kumar C Siddegowda, Mostafa A S Hammam, Kenji Monde

  ACS omega 3 1 753 - 759 2018年01月31日 [査読有り][通常論文]
   

  Sphingoid bases, which have a 2-amino-1,3-diol common functional group, are the structural backbone units of all sphingolipids. Recently, much attention has been focused on sphingoid bases because of their potentially beneficial bioactivities toward various cancer cells as well as their dietary interest. However, low abundance and the handling complexity caused by their amphiphilic character led to very limited research on them. Glutaraldehyde has two aldehyde groups, and it reacts rapidly with the 2-amino-1,3-diol functional group of sphingosine to give a tricyclic product. Immobilization of glutaraldehyde on a resin was successfully performed by organic synthesis, starting from trans-p-coumaric acid via eight steps. This approach suppresses the self-polymerization of glutaraldehyde, and addition of water to the developed resin causes the formation of cyclic double hemiacetal function, which avoids oxidation like a reducing sugar in nature and makes it stable even for up to 1 year incubation. The resin was applied to the solid-phase extracting experiment of free sphingosine from human serum at a concentration of 280 nM. Another extraction study of edible golden oyster mushrooms showed that the sphingoid base was selectively captured from complex natural extracts. These results demonstrate that the developed glutaraldehyde resin method is a highly selective method, and hence, the combination of it with the o-phthaldialdehyde HPLC method was confirmed as an efficient and sensitive method for analysis of sphingoid bases in biological samples.
• Focused Genome Mining of Structurally Related Sesterterpenes: Enzymatic Formation of Enantiomeric and Diastereomeric Products

  Koji Narita, Hajime Sato, Atsushi Minami, Kosei Kudo, Lei Gao, Chengwei Liu, Taro Ozaki, Motoichiro Kodama, Xiaoguang Lei, Tohru Taniguchi, Kenji Monde, Mami Yamazaki, Masanobu Uchiyama, Hideaki Oikawa

  ORGANIC LETTERS 19 24 6696 - 6699 2017年12月 [査読有り][通常論文]
   

  Heterologous expression of four Glade-A bifunctional terpene synthases (BFTSs), giving di/sesterterpenes with unique polycyclic carbon skeletons such as sesterfisherol, enabled the isolation of the sesterterpenes Bm1, Bm2, Bm3, and Ph1. Their structures suggested that formation of the products occurs via various diastereomeric carbocation intermediates, allowing the proposal that dade-A BFTSs catalyze three-step cyclizations using several stereofacial combinations of allylic cation-olefin pairs in the corresponding intermediates to generate various stereoisomers.
• Asymmetric Synthesis of β-Lactams through Copper-Catalyzed Alkyne-Nitrone Coupling with Prolinol-Phosphine Chiral Ligand

  Takayama Y, Ishii T, Ohmiya H, Iwai T, Schwarzer M. C, Mori S, Taniguchi T, Monde K, Sawamura M

  Chem. Eur. J. 23 35 8400 - 8404 2017年06月 [査読有り][通常論文]
   

  Prolinol-phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne-nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral beta-lactams. A high level of enantiocontrol was achieved not only with aryl-or alkenylacetylenes but also with alkylacetylenes, which were important but unfavorable substrates in the previously reported protocols. Two-point hydrogen bonding between the chiral ligand and the nitrone oxyanion consisting of O-H center dot center dot center dot O and C(sp(3)) H center dot center dot center dot O hydrogen bonds is proposed.
• Practical Use of Circular Dichroism and Vibrational Circular Dichroism for Structural Analysis

  Tohru Taniguchi, Kenji Monde

  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 75 5 522 - 529 2017年05月 [査読有り][通常論文]
   

  The use of theoretical calculations of circular dichroism (CD) and vibrational circular dichroism (VCD) spectroscopies for structural analysis has been becoming popular among organic chemists. In association with the conventional CD exciton chirality method and a recently-developed VCD exciton chirality method, proper use of CD and VCD spectroscopies should advance various studies related to chirality. This article briefly discusses the basics of structural analysis using theoretical calculations and the exciton chirality method of CD and VCD, with some tips and cautions for reliable spectral interpretation. The latter half of this article is dedicated to describing recent examples of the use of VCD for analyzing the configuration and conformation of small molecules, polymers, supramolecules, etc.
• Formal (4+1) Cycloaddition and Enantioselective Michael–Henry Cascade Reactions To Synthesize Spiro[4,5]decanes and Spirooxindole Polycycles

  Huang, J.-R, Sohail, M, Taniguchi, T, Monde, K, Fujie Tanaka

  Angew. Chem., Int. Ed. 56 21 5853 - 5857 2017年05月 [査読有り][通常論文]
   

  Spiro[4,5]decanes and polycyclic compounds bearing spiro[4,5] decane systems are important biofunctional molecules. Described are diastereoselective formal (4+1)cycloaddition reactions to afford oxindole-functionalized spiro[4,5]decanes and organocatalytic enantioselective Michael-Henry cascade reactions of the (4+1) cycloaddition products to generate spirooxindole polycyclic derivatives bearing the spiro[4,5]decane system. Spiro[4,5]decanes bearing oxindoles containing three stereogenic centers and spirooxindole polycycles having seven stereogenic centers, including two all-carbon chiral quaternary centers and one tetrasubstituted chiral carbon center, were obtained with high diastereo- and enantioselectivities.
• Synthesis of Nontoxic Fluorous Sphingolipids as Molecular Probes of Exogenous Metabolic Studies for Rapid Enrichment by Fluorous Solid Phase Extraction

  Shota Saito, Yuta Murai, Seigo Usuki, Masafumi Yoshida, Mostafa A. S. Hammam, Susumu Mitsutake, Kohei Yuyama, Yasuyuki Igarashi, Kenji Monde

  EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2017 6 1045 - 1051 2017年02月 [査読有り][通常論文]
   

  Fluorous solid-phase extraction (FSPE) is a useful technique for efficient selective enrichment of fluorous compounds from nonfluorous molecules. Sphingolipids and their metabolites, which are ubiquitous building blocks of eukaryotic and prokaryotic cell membranes, play crucial roles, for example, as signaling molecules. However, details of the functions and metabolic mechanisms of exogenous sphingolipids have remained unknown compared with those of their endogenous analogs. To better understand these unknown roles, chemical probes with appropriate biological and physicochemical properties are needed. In this study, we designed and synthesized new fluorous sphingolipids to reveal these roles. Furthermore, we confirmed that they could be efficiently and rapidly separated from normal sphingolipids by FSPE, and that they hardly showed any cytotoxic activity, similarly to normal sphingolipids at the same dose. We also showed that these fluorinated ceramides could act as metabolic substrates for sphingomyelin synthase 2 (SMS2). This demonstrates their potential for further biological studies.
• 化学プローブは求愛タンパク質の心をどう射留めるのか？-生命現象解明・創薬に小分子の視点から

  門出 健次, 村井 勇太

  化学 72 10 70 - 71 2017年 [査読無し][通常論文]
  
• 円二色性(CD)・赤外円二色性(VCD)による立体構造解析 〜実践例と注意点〜

  谷口 透, 門出 健次

  有機合成化学協会誌 75 522 - 529 2017年 [査読無し][通常論文]
  
• Analysis of Configuration and Conformation of Furanose Ring in Carbohydrate and Nucleoside by Vibrational Circular Dichroism

  Tohru Taniguchi, Kie Nakano, Ryosuke Baba, Kenji Monde

  ORGANIC LETTERS 19 2 404 - 407 2017年01月 [査読有り][通常論文]
   

  A reliable and convenient method for determining the configuration and conformation of the furanose ring in carbohydrates and nucleosides by vibrational circular dichroism (VCD) spectroscopy is described. Diastereomeric pairs of several furanose monosaccharides and nucleosides were prepared, and their VCD spectra were analyzed. The results revealed that VCD spectroscopy elucidates the equibrated state of the furanose ring puckers, which is often difficult to study by other techniques.
• α-Arylation of α-Amino Acid Derivatives with Arynes via Memory of Chirality: Asymmetric Synthesis of Benzocy-clobutenones with Tetrasubstituted Carbon

  Kasamatsu, K, Yoshimura, T, Mándi, A, Taniguchi, T, Monde, K, Furuta, T, Kawabata, T

  Org. Lett. 19 2 352 - 355 2017年01月 [査読有り][通常論文]
   

  A method for asymmetric alpha-arylation of alpha-amino acid derivatives via memory of chirality has been developed. Addition of axially chiral enolates, generated from alpha-amino acid derivatives, to in situ generated arynes, followed by intramolecular C-acylation of the resulting aryl metallic species, gave benzocyclobutenones with a tetrasubstituted carbon with retention of configuration in up to 99% ee.
• Reinvestigation of the Absolute Configurations of Chiral ß-Mercaptoalkanones Using Vibrational Circular Dichroism and 1H NMR Analysis

  Kiske, C, Noerenberg, S, Ecker, M, Ma, X, Taniguchi, T, Monde, K, Eisenreich, W, Engel, K.-H

  J. Agric. Food Chem. 64 45 8563 - 8571 2016年11月 [査読有り][通常論文]
   

  The absolute configurations of chiral beta-mercaptoalkanones were previously assigned on the basis of the H-1 NMR anisotropy method using (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-M alpha NP) as the chiral auxiliary. This study presents a reinvestigation of the configurations of 4-mercapto-2-pentanone 1, 4-mercapto-2-heptanone 2, and 2-mercapto-4-heptanone 3. Enantiomers of 1, 2, and 3 were obtained by lipase-catalyzed hydrolyses of the respective acetylthioalkanones. Upon derivatization with (S)-M alpha NP, the configurations of the reaction products were deduced based on the order of the HPLC elution of the diastereoisomeric thioesters, assuming that the sector rule previously developed for secondary alcohols is also valid for thiols. In addition, the configurations were experimentally determined by vibrational circular dichroism (VCD) and ill NMR analyses after esterification with (R)-hydratropic acid (HTA) and 2-methoxy-2-phenylacetic acid (MPA). The assignments of the configurations using VCD and NMR analyses of HTA- and MPA-thioesters were in agreement. However, they were opposite to those deduced for (S)-M alpha NP thioesters via the sector rule. Consequently, the formerly assigned configurations of beta-mercaptoalkanones deduced via investigation of (S)-M alpha NP-derivatives have to be revised.
• Asymmetric Diels–Alder Reaction of α-Substituted and β,β-Disubstituted α,β-Enals via Diarylprolinol Silyl Ether for the Construction of All-Carbon Quaternary Stereocenters

  Hayashi, Y, Bondzic, B. P, Yamazaki, T, Gupta, Y, Ogasawara, S, Taniguchi, T, Monde, K

  Chem., Eur. J. 22 44 15874 - 15880 2016年10月 [査読有り][通常論文]
   

  The asymmetric Diels-Alder reaction of -substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl-substituted diarylprolinol silyl ether to afford the exo-isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels-Alder reaction of a ,-disubstituted ,-unsaturated aldehyde, good exo-selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all-carbon quaternary stereocenters are constructed enantioselectively.
• Studying the stereostructures of biomolecules and their analogs by vibrational circular dichroism

  Tohru Taniguchi, Takahiro Hongen, Kenji Monde

  POLYMER JOURNAL 48 9 925 - 931 2016年09月 [査読有り][招待有り]
   

  The functions of biomacromolecules are largely governed by their stereostructure (i.e., configuration and conformation). Therefore, detailed understanding of their structural properties should help in regulating the functions of artificial macromolecules. However, studying the stereostructure of a molecule in the solution state is typically difficult due to the lack of suitable analytical techniques. Vibrational circular dichroism (VCD) spectroscopy, which measures circular dichroism in the infrared region, exhibits high sensitivity toward molecular stereostructures. In this paper, we first discuss a method for the elucidation of the stereostructures of small to large molecules based on theoretical calculations of VCD. The rest of the paper is dedicated to the applications of a VCD exciton chirality method, a novel approach recently developed by the authors to interpret VCD data by observing a VCD couplet in the C=O stretching region, to various biomolecules such as peptides, carbohydrates, polyesters and lipids.
• A Bioinspired Synthesis of (±)-Rubrobramide, (±)-Flavipucine, and Isoflavipucine

  Mizutani, S, Komori, K, Taniguchi, T, Monde, K, Kuramochi, K, Tsubak, K

  Angew. Chem., Int. Ed. 55 33 9553 - 9556 2016年08月 [査読有り][通常論文]
   

  A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an alpha-bromo-beta-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an a, beta-epoxy-gamma-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (+/-)-Flavipucine and (+/-)-isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected a-bromo-b-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (+/-)-flavipucine, which was converted into (+/-)-isoflavipucine by thermal isomerization.
• Facile Diastereoseparation of Glycosyl Sulfoxides by Chiral Stationary Phase

  Tohru Taniguchi, Mai Asahata, Akihito Nasu, Yukatsu Shichibu, Katsuaki Konishi, Kenji Monde

  CHIRALITY 28 7 534 - 539 2016年07月 [査読有り][通常論文]
   

  Separation of the diastereomers of glycosyl sulfoxides differing in the sulfur chirality has been difficult. This article presents a fast and scalable method for their diastereoseparation using a chiral stationary phase. The usefulness of this method was demonstrated in a 500-mg scale separation within 20 min, and in the separation of trisaccharyl sulfoxide diastereomers. (C) 2016 Wiley Periodicals, Inc.
• Reducing Molecular Flexibility by Cyclization for Elucidation of Absolute Configuration by CD Calculations: Daurichromenic Acid

  Attila Mandi, Mahadeva M. M. Swamy, Tohru Taniguchi, Masaki Anetai, Kenji Monde

  CHIRALITY 28 6 453 - 459 2016年06月 [査読有り][通常論文]
   

  Circular dichroism (CD) calculations of flexible natural products have been difficult because of the large number of low-energy conformers and ambiguous Boltzmann distributions. In this article, through electronic (ECD) and vibrational (VCD) studies on a natural product, (+)-daurichromenic acid, we demonstrate that derivatization of a flexible molecule can dramatically reduce its flexibility. This work also shows the usefulness of derivatization for diminishing computational expenses required for optimization and CD calculations, and for increasing the reliability of the assignment of absolute configuration. Chirality 28:453-459, 2016. (c) 2016 Wiley Periodicals, Inc.
• Stereochemical Study of Sphingosine by Vibrational Circular Dichroism

  Atsufumi Nakahashi, Ananda Kumar C. Siddegowda, Mostafa A. S. Hammam, Siddabasave Gowda B. Gowda, Yuta Murai, Kenji Monde

  ORGANIC LETTERS 18 10 2327 - 2330 2016年05月 [査読有り][通常論文]
   

  Vibrational circular dichroism (VCD) was first applied to the stereochemical analysis of sphingosine. VCD patterns derived from the C=C stretch as well as other mid-infrared (IR) regions were practical markers to discriminate all the stereoisomers of intact sphingosine. Glutaraldehyde was found as an excellent derivatizing reagent for sphingosine which improves its solubility in VCD-friendly nonpolar solvents such as chloroform and enhances the VCD intensities by forming a rigid cyclized structure.
• Efficient Synthesis of Photoreactive 2-Propoxyaniline Derivatives as Artificial Sweeteners

  Yuta Murai, Takuma Yoshida, Lei Wang, Katsuyoshi Masuda, Yasuyuki Hashidoko, Kenji Monde, Yasumaru Hatanaka, Makoto Hashimoto

  SYNLETT 27 6 946 - 950 2016年04月 [査読有り][通常論文]
   

  5-Nitro-2-propoxyaniline is one of the strongest artificial sweeteners. However, little is known about the detailed relationship of the structure and biological activity between 5-nitro-2-propoxyaniline and its sweet receptor. Photoaffinity labeling is a useful method for revealing interactions of a small bioactive compound with molecules. Therefore, we synthesized photoreactive 2-propoxyaniline derivatives as useful tools for revealing the interactions by photoaffinity labeling.
• Enantioselective Synthesis of Aminoindan Carboxylic Acid Derivatives by the Catalytic Intramolecular [2+2+2] Cycloaddition of Amino-Acid-Tethered Triynes

  Yu-ki Tahara, Shuhei Obinata, Kyalo Stephen Kanyiva, Takanori Shibata, Attila Mandi, Tohru Taniguchi, Kenji Monde

  EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2016 7 1405 - 1413 2016年03月 [査読有り][通常論文]
   

  The enantioselective synthesis of aminoindan carboxylic acid (Aic) derivatives was achieved by Rh-catalyzed intramolecular [2+2+2] cycloaddition of amino-acid-tethered triynes. This reaction, along with recrystallization, gave chiral tethered Aic derivatives with excellent enantiomeric excess. Subsequent hydrolysis of the tethered Aic compounds afforded chiral Aic derivatives, which were further transformed into a free Aic and its dimethyl ester in good yields.
• What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor?

  Mikako Kato, Mostafa A. S. Hammam, Tohru Taniguchi, Yoshiko Suga, Kenji Monde

  ORGANIC LETTERS 18 4 768 - 771 2016年02月 [査読有り][通常論文]
   

  D609 (1) has been, used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed,. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities.
• Stereochemistry of a Rhododaurichromanic Acid Derivative

  Mahadeva M. M. Swamy, Attila Mandi, Masaki Anetai, Kenji Monde

  NATURAL PRODUCT COMMUNICATIONS 11 2 193 - 195 2016年02月 [査読有り][通常論文]
   

  A rhododaurichromanic acid A derivative was synthesized from the naturally occurring daurichromenic acid in enantiomeric pure form. Its absolute configuration was elucidated by applying VCD, ECD and DFT calculations.
• Highly efficient preparation of sphingoid bases from glucosylceramides by chemoenzymatic method

  Siddabasave B. Gowda Gowda, Seigo Usuki, Mostafa A. S. Hammam, Yuta Murai, Yasuyuki Igarashi, Kenji Monde

  JOURNAL OF LIPID RESEARCH 57 2 325 - 331 2016年02月 [査読有り][通常論文]
   

  Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond beta-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield.
• VCD励起子キラリティー法

  門出 健次, 谷口 透

  分光研究 65 2 137 - 144 日本分光学会 2016年 [査読無し][通常論文]
  
• Hydrogen Bonding to Carbonyl Oxygen of Nitrogen-Pyramidalized Amide – Detection of Pyramidalization Direction Preference by Vibrational Circular Dichroism Spectroscopy

  Wang, S, Taniguchi, T, Monde, K, Kawahata, M, Yamaguchi, K, Otani, Y, Ohwada T

  Chem. Commun. 52 21 4018 - 4021 2016年 [査読有り][通常論文]
   

  Nitrogen-pyramidalization of amide increases electron density on nitrogen and decreases that on carbonyl oxygen. We identified hydrogen-bonding to carbonyl of nitrogen-pyramidalized bicyclic beta-proline derivatives by crystallography, and by NMR and vibrational circular dichroism (VCD) spectroscopy in solution. Such hydrogen-bonding can switch the preferred nitrogen-pyramidalization direction, as detected by VCD spectroscopy.
• Epigenetic stimulation of polyketide production in Chaetomium cancroideum by an NAD(+)-dependent HDAC inhibitor

  Teigo Asai, Shuntaro Morita, Tohru Taniguchi, Kenji Monde, Yoshiteru Oshima

  ORGANIC & BIOMOLECULAR CHEMISTRY 14 2 646 - 651 2016年 [査読有り][通常論文]
   

  Exposure of the fungus Chaetomium cancroideum to an NAD(+)-dependent HDAC inhibitor, nicotinamide, enhanced the production of aromatic and branched aliphatic polyketides, which allowed us to isolate new secondary metabolites, chaetophenol G and cancrolides A and B. Their structures were determined using spectroscopic analyses, and their absolute configuration was elucidated by electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and chemical transformations. Biosynthesis of the branched aliphatic polyketide skeletons in cancrolides A and B was evidenced by conducting a feeding experiment using compounds labeled with a C-13 stable isotope.
• Stereochemical Analysis of Glycerophospholipids by Vibrational Circular Dichroism

  Tohru Taniguchi, Daisuke Manai, Masataka Shibata, Yutaka Itabashi, Kenji Monde

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 137 38 12191 - 12194 2015年09月 [査読有り][通常論文]
   

  The stereochemistry of glycerophospholipids (GPLs) has been of interest for its roles in the evolution of life and in their biological activity. However, because of their structural complexity, no convenient method to determine their configuration has been reported. In this work, through the first systematic application of vibrational circular dichroism (VCD) spectroscopy to various diacylated GPLs, we have revealed that their chirality can be assigned by the sign of a VCD exciton couplet generated by the interaction of two carbonyl groups. This paper also presents spectroscopic evidence for the stereochemistry of GPLs isolated from bacteria, eukaryotes, and mitochondria.
• Genome Mining for Sesterterpenes Using Bifunctional Terpene Synthases Reveals a Unified Intermediate of Di/Sesterterpenes

  Ying Ye, Atsushi Minami, Attila Mandi, Chengwei Liu, Tohru Taniguchi, Tomohisa Kuzuyama, Kenji Monde, Katsuya Gomi, Hideaki Oikawa

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 137 36 11846 - 11853 2015年09月 [査読有り][通常論文]
   

  Genome mining is a promising method to discover novel secondary metabolites in the postgenomic era. We applied the Aspergillus oryzae heterologous expression system to functionally characterize cryptic bifunctional terpene synthase genes found in fungal genomes and identified the sesterfisherol synthase gene (NfSS) from Neosartorya fischeri. Sesterfisherol contains a characteristic 5-6-8-5 tetracyclic ring system and is modified by cytochrome P450 monooxygenase (NfP450) to sesterfisheric acid. The cyclization mechanism was proposed on the basis of the analysis of in vivo and in vitro enzymatic reactions with isotopically labeled precursors. The mechanism involves Cl cation-olefin IV-olefin V cyclization followed by five hydride shifts, allowing us to propose a unified biogenesis for sesterterpenes branching from bicyclic (5-15), tricyclic (5-12-5), and tetracyclic (5-6-8-5) cation intermediates. Furthermore, the mechanism is distinct from that of a separate class of di/sesterterpenes including fusicoccins and ophiobolins. The difference between mechanisms is consistent with phylogenetic analysis of bifunctional terpene synthases, suggesting that the amino acid sequence reflects the initial cyclization mode, which is most likely related to the initial conformation of a linear prenyl diphosphate.
• Asymmetric Nitrocyclopropanation of α-Substituted α,β-Enals Catalyzed by Diphenylprolinol Silyl Ether for the Construction of All-Carbon Quaternary Stereogenic Centers.

  Hayashi, Y, Yamazaki, T, Nakanishi, Y, Ono, T, Taniguchi,T, Monde, K, Uchimaru,T

  Eur.J. Org. Chem. 2015 26 5747 - 5754 2015年09月 [査読有り][通常論文]
   

  The diphenylprolinol silyl ether mediated asymmetric nitrocyclopropanation of -substituted ,-unsaturated aldehydes with bromonitromethane, followed by base-promoted isomerization was found to afford trans-nitrocyclopropanecarbaldehydes with all-carbon quaternary stereogenic centers with excellent diastereo- and enantioselectivities. DFT calculations indicated that the s-trans conformer of the iminium ion intermediate is more stable than the s-cis conformer. In addition, nucleophilic attack of the bromonitromethane anion to the iminium ion intermediate was calculated to occur preferentially from the opposite side of the bulky substituents of the pyrrolidine iminium intermediate.
• Vibrational CD (VCD) Spectroscopy as a Powerful Tool for Chiral Analysis of Flavor Compounds

  Yoshihiro Yaguchi, Atsufumi Nakahashi, Nobuaki Miura, Tohru Taniguchi, Daisuke Sugimoto, Makoto Emura, Kyoko Zaizen, Yumi Kusano, Kenji Monde

  IMPORTANCE OF CHIRALITY TO FLAVOR COMPOUNDS 1212 35 - 56 2015年 [査読有り][通常論文]
   

  Several flavor compounds have chiral centers in their structures, and it has been shown that there are differences in odor characteristics and odor thresholds between enantiomers. Vibrational CD (VCD) is a recently developed technique for the determination of the absolute stereochemistry of organic compounds assisted by ab initio quantum theoretical calculations. In this study, the VCD technique was at first applied to patchoulol, a rigid and fused tricyclic sesquiterpene alcohol. The absolute stereochemistry proposed from the observed and calculated VCD data was in agreement with the configuration reported for patchoulol. Moreover, this method was extended to odor-active flavorous furanones having a unique keto-enol tautomeric structure that is prone to racemization. The absolute stereochemistry of flavorous 2- or 5-substituted furanones such as 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF, furaneol), 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF, mesifuran), 4-acetoxy-2,5-dimethyl-3(2H)-furanone (ADMF, furaneol acetate), 4,5-dimethyl-3-hydroxy-2(5H)-furanone (sotolon), and 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone (maple furanone) was investigated. The examples show that the VCD technique is a very powerful tool for the determination of the absolute stereochemistry of flavor compounds.
• Revision of the relative and absolute stereochemistry of 3-hydroxydehydroiso-α-lapachone and its derivatives.

  Khandelwal, P, Singh, P, Taniguchi, T, Monde, K, Johmoto, K, Uekusa, H, Masubuti, H, Fujimoto, Y

  Phytochemistry Lett. 10 224 - 229 2014年12月 [査読有り][通常論文]
   

  Rare derivatives of dehydroiso-alpha-lapachone, 3-hydroxydehydroiso-alpha-lapachone (1) and 3,8-dihydrox-ydehydroiso- alpha-lapachone (2) along with 5-hydroxydehydroiso-alpha-lapachone, 5-methoxy-dehydroisoa-alpha-lapachone, and 8-methoxy-dehydroiso-alpha-lapachone were isolated from a chloroform extract of the heartwood of Heterophragma adenophyllum (Bignoniaceae). A reinvestigation of the structures of 1 and 2 using NMR spectroscopic analysis and Mosher's method, combined with a vibrational circular dichroism (VCD) method and X-ray analysis for 1, indicated that the cis-orientation of the isopropenyl and OH groups originally assigned for 1 and 2 needs to be revised to the trans-orientation. Furthermore, the previously assigned R configuration at C-3 of 1 and 2 must be corrected as the S configuration. (C) 2014 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
• Stereoselective synthesis of 1-methoxyspiroindoline phytoalexins and their amino analogues

  Aneta Salayova, Zuzana Kudlickova, Matej Balaz, Mariana Budovska, Martina Pilatova, Jan Mojzis, Kenji Monde, Jan Petrovaj, Tatana Gondova

  TETRAHEDRON-ASYMMETRY 25 16-17 1221 - 1233 2014年09月 [査読有り][通常論文]
   

  The stereoselective synthesis of the spiroindoline phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(-)-enantiomer were achieved by the bromine-induced spirocyclization of 1-methoxybrassinin using chiral auxiliaries (+)- and (-)-menthol, followed by oxidation of the obtained menthyl ethers. The TFA-catalyzed methanolysis of chiral 1-methoxyspirobrassinol menthyl ethers provided (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether and its other three unnatural stereoisomers. The enantiomers of the 2-amino analogues of the indole phytoalexin (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether were prepared by the TFA-catalyzed replacement of the chiral alkoxy group with an amine. The synthesized compounds were tested in vitro on cancer cell lines and examined with enantiopure 2-amino analogues of the indole phytoalexin (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether, which showed in most cases, lower activity than the corresponding racemates. (C) 2014 Elsevier Ltd. All rights reserved.
• In Depth Study on Solution-State Structure of Poly(lactic acid) by Vibrational Circular Dichroism

  Takahiro Hongen, Tohru Taniguchi, Shintaro Nomura, Jun-ichi Kadokawa, Kenji Monde

  MACROMOLECULES 47 15 5313 - 5319 2014年08月 [査読有り][通常論文]
   

  Polyesters are biodegradable analogues of polypeptides, but their biochemical applications have been hampered by the lack of a method to analyze polyester conformation in a solution state. We have demonstrated that vibrational circular dichroism (VCD) spectroscopy can conveniently and accurately elucidate the conformation of polyesters through the studies on poly(L-lactic acid) (PLLA), PLLA-amylose complex, and oligo(L-lactic acid). The analysis of VCD exciton couplet of these molecules has clarified the stable left-handed helical structure of PLLA, while density functional theory calculations of oligo(L-lactic acid) have revealed its detailed structural nature.
• ENANTIOSELECTIVE INTRAMOLECULAR AZA-SPIROANNULATION ONTO BENZOFURANS USING CHIRAL RHODIUM CATALYSIS

  Takuro Shibuta, Shigeki Sato, Masatoshi Shibuya, Naoki Kanoh, Tohru Taniguchi, Kenji Monde, Yoshiharu Iwabuchi

  HETEROCYCLES 89 3 631 - 639 2014年03月 [査読有り][通常論文]
   

  The development of efficient and enantioselective intramolecular aza-spiroannulation onto benzofurans using chiral rhodium catalysis is described. The optimized reaction conditions [Rh-2(S-TCPTAD)(4) (3 mol %), PhIO (1.6 equiv), MeOH (10 equiv) in PhCF3, 0 degrees C] brought about oxidative aza-spiroannulation of 3-(carbamoylmethyl)benzofuran (3) resulting in (2R,3S)-2-methoxy-2H-spiro-[benzofuran-3,4'-oxazolidin]-2'-one (15a) in 69% yield with 86% ee, the absolute structure of which was determined by a combination of X-ray crystallography and vibrational circular dichroism (VCD) spectroscopy. The reaction is applicable to the asymmetric construction of various 2,3-dihydrobenzofuran derivatives bearing a nitrogen-containing tetrasubstituted carbon stereocenter at C3 (up to 92% ee).
• Short Synthesis of Berkeleyamide D and Determination of the Absolute Configuration by the Vibrational Circular Dichroism Exciton Chirality Method

  Kenta Komori, Tohru Taniguchi, Shoma Mizutani, Kenji Monde, Kouji Kuramochi, Kazunori Tsubaki

  ORGANIC LETTERS 16 5 1386 - 1389 2014年03月 [査読有り][通常論文]
   

  The first synthesis of (+/-)-berkeleyarnide D has been accomplished. The key features of this synthesis include the formation of an alpha,beta-epoxy-gamma-lactam via a Darzens reaction and the construction of a spirocyclic ring system by a C-acylation reaction followed by an intramolecular spirocyclization via an epoxide-opening reaction. Following optical resolution by chiral HPLC, the absolute configurations of both enantiomers of berkeleyamide D were determined by the vibrational circular dichroism exciton chirality method.
• Structures of Spiroindicumides A and B, Unprecedented Carbon Skeletal Spirolactones, and Determination of the Absolute Configuration by Vibrational Circular Dichroism Exciton Approach

  Teigo Asai, Tohru Taniguchi, Takashi Yamamoto, Kenji Monde, Yoshiteru Oshima

  ORGANIC LETTERS 15 17 4320 - 4323 2013年09月 [査読有り][通常論文]
   

  Spiroindicumides A (1) and B (2), novel spirolactone polyketides, were isolated from a filamentous fungus, Chaetomium indicum, cultivated in the presence of a histone deacetylase inhibitor. Their structures including relative configurations were determined by spectroscopic analyses. Their absolute configurations were unambiguously assigned by the vibrational circular dichroism (VCD) exciton chirality method using only ca. 0.3 mg of each sample. This study presents the first application of the VCD exciton approach to novel natural products. A possible biosynthetic pathway of the new compounds was also proposed.
• Structurally Diverse Chaetophenol Productions Induced by Chemically Mediated Epigenetic Manipulation of Fungal Gene Expression

  Teigo Asai, Takashi Yamamoto, Naoki Shirata, Tohru Taniguchi, Kenji Monde, Isao Fujii, Katsuya Gomi, Yoshiteru Oshima

  ORGANIC LETTERS 15 13 3346 - 3349 2013年07月 [査読有り][通常論文]
   

  Epigenetic manipulation of gene expression in Chaetomium indicum using a HDAC inhibitor led to the isolation of structurally diverse chaetophenols, and 3, 4 and 5 bear unprecedented polycyclic skeletons. The expression of two silent genes (pksCH-1 and pksCH-2) for nonreducing PKSs involved in chaetophenol biosynthesis was associated with an increase of histone acetylation level. The heterologous gene expression study in Aspergillus oryzae revealed pksCH-2 to be the NR-PKS gene for 8.
• Structures and absolute configurations of short-branched fatty acid dimers from an endophytic fungus of Aloe arborescens

  Teigo Asai, Sae Otsuki, Tohru Taniguchi, Kenji Monde, Kouwa Yamashita, Hiroaki Sakurai, Tomoji Ozeki, Yoshiteru Oshima

  TETRAHEDRON LETTERS 54 26 3402 - 3405 2013年06月 [査読有り][通常論文]
   

  Mycosphines A-D (1-4), comprising a class of new short-branched fatty acid dimers, were found in the cultures of an endophytic fungus, Mycosphaerella sp., isolated from Aloe arborescens. The structures, including the absolute stereochemistries were determined by spectroscopic analysis, single crystal Xray diffraction, and vibrational circular dichroism (VCD). (C) 2013 Elsevier Ltd. All rights reserved.
• 糸状菌二次代謝を活性化するNAD依存型HDAC阻害剤の探索とそれを用いた新規天然物の創出

  森田 峻太郎, 浅井 禎吾, 谷口 透, 門出 健次, 櫻井 博章, 尾関 智二, 山下 幸和, 大島 吉輝

  日本薬学会年会要旨集 133年会 2 177 - 177 (公社)日本薬学会 2013年03月 [査読有り][通常論文]
  
• Structural Diversity of New C-13-Polyketides Produced by Chaetomium mollipilium Cultivated in the Presence of a NAD(+)-Dependent Histone Deacetylase Inhibitor

  Teigo Asai, Shuntaro Morita, Naoki Shirata, Tohru Taniguchi, Kenji Monde, Hiroaki Sakurai, Tomoji Ozeki, Yoshiteru Oshima

  ORGANIC LETTERS 14 21 5456 - 5459 2012年11月 [査読有り][通常論文]
   

  Cultivation of Chaetomium mollipilium with nicotinamide, a NAD(+)-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C-13-polyketides, mollipilin A-E (1-5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1-6, and plausible biosynthetic pathways for 1-7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.
• Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor

  Teigo Asai, Dan Luo, Yutaro Obara, Tohru Taniguchi, Kenji Monde, Kouwa Yamashita, Yoshiteru Oshima

  TETRAHEDRON LETTERS 53 17 2239 - 2243 2012年04月 [査読有り][通常論文]
   

  The secondary metabolite production of Cordyceps annullata, an entomopathogenic fungus, was clearly enhanced by the addition of suberoyl bis-hydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, to the culture medium. Four new 2,3-dihydrobenzofurans, annullatins A-D (1-4), and a new aromatic polyketide, annullatin E (5) were isolated from the culture medium, and the structures, including the absolute stereochemistries, were determined by spectroscopic analysis, vibrational circular dichroism (VCD), and chemical transformations. Annullatin A (1) exhibited potent agonistic activity toward the cannabinoid receptors CB1 and CB2. Annullatin B (2) and D (4) displayed CB1 agonistic activity and CB2 inverse agonistic activity. (c) 2012 Elsevier Ltd. All rights reserved.
• Enantioselective synthesis of tripodal cyclophanes and pyridinophanes by intramolecular [2+2+2] cycloaddition

  Takanori Shibata, Mayu Miyoshi, Toshifumi Uchiyama, Kohei Endo, Nobuaki Miura, Kenji Monde

  TETRAHEDRON 68 12 2679 - 2686 2012年03月 [査読有り][通常論文]
   

  An enantioselective intramolecular [2+2+2] cycloaddition of 2-aminophenol-tethered triynes and diyne-nitriles proceeded using the chiral Rh catalysts, and tripodal cyclophanes and pyridinophanes with a long ansa chain (up to [16]pyridinophane) were obtained in acceptable yield with high to almost perfect ee. In the reaction of triynes, we elucidated that the oxygen atom at the alkyne terminus is essential for the excellent enantioselectivity. For the construction of cage-type molecule, the choice of rigid tether, which connects 1,6-diyne moiety with a side carbon chain having alkyne or cyano group on its terminus, was important, and 8-amino-2-naphthol moiety was also a preferable tether. (C) 2012 Elsevier Ltd. All rights reserved.
• Optical Rotation, Electronic Circular Dichroism, and Vibrational Circular Dichroism of Carbohydrates and Glycoconjugates

  Tohru Taniguchi, Kenji Monde

  Comprehensive Chiroptical Spectroscopy 2 795 - 818 2012年02月17日 [査読有り][通常論文]
  
• Exciton Chirality Method in Vibrational Circular Dichroism

  Tohru Taniguchi, Kenji Monde

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 8 3695 - 3698 2012年02月 [査読有り][通常論文]
   

  The interaction of two IR chromophores yields a strong vibrational circular dichroism couplet whose sign reflects the absolute configuration of the molecule. We present a method to determine absolute configuration of a chiral molecule based on this couplet without need of theoretical calculation. Not only can this method analyze various molecules whose absolute configuration is difficult to determine by other spectroscopic methods, but also it can significantly enhance VCD signals.
• Salvileucalin C, a novel rearranged neoclerodane diterpene from Salvia leucantha

  Yutaka Aoyagi, Akira Yamazaki, Reiko Kato, Fukuya Tobe, Haruhiko Fukaya, Tadateru Nishikawa, Atsufumi Nakahashi, Nobuaki Miura, Kenji Monde, Koichi Takeya

  TETRAHEDRON LETTERS 52 16 1851 - 1853 2011年04月 [査読有り][通常論文]
   

  Salvileucalin C (1), a novel neoclerodane diterpene having an unprecedented carbon framework and a structurally closely related salvileucalin D (2) were isolated and their absolute structures were elucidated by the vibrational circular dichroism (VCD) spectra. (C) 2011 Elsevier Ltd. All rights reserved.
• A Vibrational Circular Dichroism Approach to the Determination of the Absolute Configurations of Flavorous 5-Substituted-2(5H)-furanones

  Atsufumi Nakahashi, Yoshihiro Yaguchi, Nobuaki Miura, Makoto Emura, Kenji Monde

  JOURNAL OF NATURAL PRODUCTS 74 4 707 - 711 2011年04月 [査読有り][通常論文]
   

  Sotolon (1) and Maple furanone (2) are naturally occurring chiral furanones. These 5-substituted-2(5H)-furanones are industrially significant aroma compounds due to their characteristic organoleptic properties, and extraordinarily low odor thresholds. Each enantiomer of 1 and 2 was successfully obtained by preparative enantioselective supercritical fluid chromatography. The absolute configuration of 1 was confirmed as (R)-(-)-1 and (S)-(+)-1 by:adopting the vibrational circular dichroism (VCD) approach. The absolute configuration of 2, which has remained ambiguous since its discovery in 1957, was determined as,(R)-(+)-2 and (S)-(-)-2 for the first tune by the VCD technique. Surprisingly, the signs of the optical rotation of 2;are opposite. of those of 1 regardless of their identical absolute configurations This observation emphasizes the risk in, absolute configurational assignments based on comparison of optical rotation signs of similar structures Odor evaluation of the enantiomers of 2 revealed different odor intensities
• (R)-(+)-[VCD(–)984]-4-Ethyl-4-methyloctane: A Cryptochiral Hydrocarbon with a Quaternary Chiral Center. (1) Synthesis of the Enantiopure Compound and Unambiguous Determination of Absolute Configuration

  Fujita T, Obata K, Kuwahara S, Nakahashi A, Monde K, Decatur J, Harada N

  Eur. J. Org. Chem. 33 33 6372 - 6384 2010年11月 [査読有り][通常論文]
   

  Enantiopure (R)-(+)-[VCD(-)984]-4-ethyl-4-methyloctane (1), a cryptochiral hydrocarbon with a quaternary chiral center, was synthesized by the use of 2-methoxy-2-(1-naphthyl)propionate (M alpha NP) and (-)-camphorsultam dichlorophthalic (CSDP) acid methods. The diastereomeric M alpha NP and CSDP acid esters prepared from racemic 2-butyl-2-methyl-1-tetralols, were effectively separated by HPLC on silica gel, and their absolute configurations were unambiguously determined by X-ray crystallographic analysis and H-1 NMR anisotropy methods. The recovered enantiopure 2-butyl-2methyl-1-tetralol [(1S,2S)-(+)-cis-9] was then converted into the hydrocarbon (+)-1, the R absolute configuration of which was unambiguously determined for the first time. The structure of hydrocarbon 1 was also confirmed by NMR HSQC-TOCSY analysis.
• (R)-(+)-[VCD(–)984]-4-Ethyl-4-methyloctane: A Cryptochiral Hydrocarbon with a Quaternary Chiral Center. (2) Vibrational CD Spectra of Both Enantiomers and Absolute Configurational Assignment

  Kuwahara S, Obata K, Fujita T, Miura N, Nakahashi A, Monde K, Harada N

  Eur. J. Org. Chem. 33 33 6385 - 6392 2010年11月 [査読有り][通常論文]
   

  To characterize precisely the chiroptical properties of 4-ethyl-4-methyloctane (1), one of the so-called cryptochiral compounds, the enantiomer (S)-(-)-[VCD(+)984]-1 was synthesized in an enantiopure form. The observed specific rotation values at 365 nm of both enantiomers agreed well, but were opposite in sign, confirming their enantiomeric relationship, although their absolute values were very small, reflecting their cryptochirality. The vibrational circular dichroism (VCD) spectra of both enantiomers were measured neat and showed characteristic Cotton effects around 1150-900 cm(-1); the VCD spectral curves were mirror images of each other. Based on the observed positive VCD band at 984 cm(-1) for (S)-(-)-1, its absolute configuration was fully designated as (S)-(-)-[VCD(+)984]-1. The VCD spectrum was quantum chemically calculated by the DFT MO method at the B3PW91/6-31G(d,p) level, and the simulated VCD curve for (S)-1 agreed very well with the observed VCD spectrum of (S)-(-)-1, confirming the absolute configuration.
• Super water- and highly oil-repellent films made of fluorinated poly(alkylpyrroles)

  Kaori Chiba, Kazutomo Kurogi, Kenji Monde, Mai Hashimoto, Masafumi Yoshida, Hiroyuki Mayama, Kaoru Tsujii

  COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS 354 1-3 234 - 239 2010年02月 [査読無し][通常論文]
   

  Super water- and highly oil-repellent films have been synthesized by electrochemical polymerization of some new monomers of fluorinated alkylpyrroles. The surface roughness of the films was controlled by the polymerization conditions such as concentration of monomers, applied voltages, polymerization time and so on. The contact angles on the most liquid-repellent film surfaces are about 160 degrees and 140 degrees for water and salad oil, respectively. The sliding angle for the salad oil is 9.5 +/- 2.5 degrees which is much better than that on the poly(alkylpyrrole) films coated with a fluorinated aikylsilane coupling agent. Thermal and organic solvent stability for the liquid-repellent property of the films were quite good to be used practically. (C) 2009 Elsevier B.V. All rights reserved.
• Stereochemical Studies of Odorous 2-Substituted-3(2H)-furanones by Vibrational Circular Dichroism

  Makoto Emura, Yoshihiro Yaguchi, Atsufumi Nakahashi, Daisuke Sugimoto, Nobuaki Miura, Kenji Monde

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 57 21 9909 - 9915 2009年11月 [査読有り][通常論文]
   

  Chiral naturally occurring aroma compounds often exhibit enantiomeric excesses due to their stereoselective biogenesis. In general, significant organoleptic differences are perceived between these enantiomers. Chiral 2-substituted-3(2H)-furanones, featuring a unique keto-enol tautomer, the cause of their racemization, have been known to play an important role in flavor because of their extremely low threshold values and their burnt sugar odor characteristics. Since the discovery of these important aroma chemicals, they have been used in large quantities as raw materials in the flavor and fragrance industry. However, absolute configurations of these furanone derivatives have remained ambiguous for the past 40 years. Here optical resolutions of 2,5-dimethyl-4-hydroxy-3(2H)-furanone 2,5-dimethyl-4-methoxy-3(2H)-furanone, and 4-acetoxy-2,5-dimethyl-3(2H)-furanone were accomplished using chiral CO(2) supercritical fluid chromatography (SFC). Their absolute configurations were unraveled for the first time using the vibrational circular dichroism (VCD) technique as well as by chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and odor activities.
• Stereochemical studies of hexylitaconic acid, an inhibitor of p53-HDM2 interaction

  Atsufumi Nakahashi, Nobuaki Miura, Kenji Monde, Sachiko Tsukamoto

  BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 19 11 3027 - 3030 2009年06月 [査読無し][通常論文]
   

  Hexylitaconic acid (1) is an intriguing natural product possessing a chiral carbon, and both its enantiomers have been found in nature. Enantiomeric pure (+)-(1) and (-)-(1) were successfully prepared by racemic synthesis followed by enantiomeric separation in a chiral HPLC system. Their absolute configurations were clarified by the vibrational circular dichroism technique using their methyl esters 2 and lactones 3. Their inhibitory activities against the interaction of p53-HDM2 were also examined. (C) 2009 Elsevier Ltd. All rights reserved.
• Vibrational CD spectroscopy as a powerful tool for stereochemical study of cyclophynes in solution

  De Lie An, Qiang Chen, Jingkun Fang, Hong Yan, Akihiro Orita, Nobuaki Miura, Atsufumi Nakahashi, Kenji Monde, Junzo Otera

  TETRAHEDRON LETTERS 50 15 1689 - 1692 2009年04月 [査読有り][通常論文]
   

  Stereochemical study of cyclophynes, which is otherwise rather difficult to perform, can be achieved by vibrational CD spectroscopy. (C) 2009 Published by Elsevier Ltd.
• Absolute Configuration of Actinophyllic Acid As Determined through Chiroptical Data

  Tohru Taniguchi, Connor L. Martin, Kenji Monde, Koji Nakanishi, Nina Berova, Larry E. Overman

  JOURNAL OF NATURAL PRODUCTS 72 3 430 - 432 2009年03月 [査読有り][通常論文]
   

  The absolute configuration of actinophyllic acid (-)-1, an alkaloid with an unprecedented 2,3,6,7,9,13c-hexahydro-1H-1,7,8-(methanetriyloxymethano)pyrrolo[1',2':1,2]azacino[4,3-b]indole-8(5H)-carboxylic acid skeleton isolated from Alstonia actinophylla, was determined through the study of its corresponding methyl ester 2. Racemic 2 was separated into (+)-2 and (-)-2 enantiomers, and they were assigned unambiguously as 15S,16R,19R,20R,21S and 15R,16S,19S,20S,21R, respectively, by the use of optical rotation and electronic circular dichroism. Finally, (-)-2 was characterized as the methyl ester of naturally occurring (-)-1. The assigned 15R,16S,19S,20S,21R-configuration of (-)-1 is consistent with a proposed biosynthetic pathway.
• Stereochemical Study of a Novel Tautomeric Furanone, Homofuraneol

  Kenji Monde, Atsufumi Nakahashi, Nobuaki Miura, Yoshihiro Yaguchi, Daisuke Sugimoto, Makoto Emura

  CHIRALITY 21 1E E110 - E115 2009年 [査読無し][通常論文]
   

  A mixture of tautomers with unique keto-enol structures, 5-ethyl-4-hydroxy-2-methylfuran-3(2H)-one and 2-ethyl-4-hydroxy-5-methylfuran-3(2H)-one (EHMF, homofuraneol, 1a and 1b), comprises four structural isomers including their enantiomers. The four isomers were successfully separated by chromatographic optical resolution, and their odor evaluation was performed. Determination of the absolute chemistry of 1a and 1b were accomplished for the first time by direct measurement of the VCD spectra of their methyl ether derivatives 4a and 4b compared with the calculated ones as well as chemical relay reaction. The relationship between odor characteristics and stereochemistry was also examined. Chirality 21:E110-E115, 2009. (C) 2009 Wiley-Liss, Inc.
• Alterations in the glycoform of cisplatin-resistant human carcinoma cells are caused by defects in the endoplasmic reticulum-associated degradation system

  Hiroaki Nakagawa, Miki Ohira, Shunji Hayashi, Shigeaki Abe, Shin Saito, Noriko Nagahori, Kenji Monde, Yasuro Shinohara, Naoki Fujitani, Hirosato Kondo, Shin-Ichi Akiyama, Akira Nakagawara, Shin-Ichiro Nishimura

  CANCER LETTERS 270 2 295 - 301 2008年11月 [査読無し][通常論文]
   

  Cisplatin, cis-diamineplatinum-(II) dichloride (CDDP), is one of the most common and valuable chemotherapeutic reagents for various cancers. However, it is well known that tumor cells gain acquired or intrinsic resistance to treatment by this anti-cancer reagent. In spite of extensive efforts using genetic and proteomic approaches, the mechanism underlying CDDP resistance remains unclear. In the present study, we report drastic structural changes in the N-glycans of glycoproteins in CDDP-resistant tumor cells (the KCP-4 cell line obtained from KB-3-1 human carcinoma cells). It was suggested that the CDDP-resistant cells exhibited an increase in one of the high-mannose-type glycans, particularly M8.1. This N-glycan is well known as a tag for the transport of unfolded protein from the endoplasmic reticulum to the lysosome, a process known as endoplasmic reticulum-associated degradation (ERAD) system. The revertant cells (KCP-4R) obtained from the KCP-4 cell line showed almost the same glycoform profile as that of the parental cells, suggesting that N-glycan biosynthesis in tumor cells clearly corresponds to the alteration in the sensitivity against CDDP. Gene expression analysis using a cDNA microarray showed a decrease in the expression of major histocompatibility complex (MHC) proteins in the resistant cells. MHC proteins form a complex with lysosome-degradated proteins and are presented on the cell surface. These results suggest that CDDP tolerance in KCP-4 cells is caused by a defect in the ERAD system. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
• Stereochemical Study of Chiral Tautomeric Flavorous Furanones by Vibrational Circular Dichroism

  Yoshihiro Yaguchi, Atsufumi Nakahashi, Nobuaki Miura, Daisuke Sugimoto, Kenji Monde, Makoto Emura

  ORGANIC LETTERS 10 21 4883 - 4885 2008年11月 [査読無し][通常論文]
   

  2-Substituted-3(2H)-furanone derivatives are industrially significant aroma compounds possessing a unique keto-enol tautomeric feature causing their racemization. Absolute configurations of two flavorous furanones, which have remained unclear for the past 40 years since their discovery, were clarified by the vibrational circular dichroism technique as well as chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and their odor activities.
• Observation and characterization of a specific vibrational circular dichroism band in phenyl glycosides

  Tohru Taniguchi, Ikuko Tone, Kenji Monde

  CHIRALITY 20 3-4 446 - 453 2008年03月 [査読無し][通常論文]
   

  Application of vibrational circular dichroism (VCD) spectroscopy to structural analysis of carbohydrates has recently progressed. However, few studies on glycoconjugates VCD have thus far been reported, despite the fact that naturally occurring carbohydrates exist as various glycoconjugates. To further explore the application of the VCD technique, we have measured a series of aromatic glycosides and found that axial aromatic glycosides exhibited a negative band at around 1230 cm(-1) while equatorial ones showed flat features in this region. This is the first structure-spectra relationship on glycoconjugate VCD that distinguishes the stereochemistry of the sugar anomers. Several model compounds were prepared and their vibrational properties calculated by using the density functional theory (DFT) method, which assigned the vibrational mode of this band based on the stretching motion of the glycosidic oxygen and aromatic carbon. This concept that aglycan parts can reflect stereochemical information of sugar moieties may encourage further VCD studies on glycoconjugates to realize practical structural analysis of carbohydrates.
• Glycoconjugate Data Bank : Structures - an annotated glycan structure database and N-glycan primary structure verification service

  Taku Nakahara, Ryo Hashimoto, Hiroaki Nakagawa, Kenji Monde, Nobuaki Miura, Shin-Ichiro Nishimura

  NUCLEIC ACIDS RESEARCH 36 D368 - D371 2008年01月 [査読無し][通常論文]
   

  Glycobiology has been brought to public attention as a frontier in the post-genomic era. Structural information about glycans has been accumulating in the Protein Data Bank (PDB) for years. It has been recognized, however, that there are many questionable glycan models in the PDB. A tool for verifying the primary structures of glycan 3D structures is evidently required, yet there have been no such publicly available tools. The Glycoconjugate Data Bank: Structures (GDB:Structures, http://www.glycostructures.jp) is an annotated glycan structure database, which also provides an N-glycan primary structure (or glycoform) verification service. All the glycan 3D structures are detected and annotated by an in-house program named 'getCARBO'. When an N-glycan is detected in a query coordinate by getCARBO, the primary structure of the glycan is compared with the most similar entry in the glycan primary structure database (KEGG GLYCAN), and unmatched substructure(s) are indicated if observed. The results of getCARBO are stored and presented in GDB: Structures.
• Chiral sulfinates studied by optical rotation, ECD and VCD: the absolute configuration of a cruciferous phytoalexin brassicanal C

  Tohru Taniguchi, Kenji Monde, Koji Nakanishi, Nina Berova

  ORGANIC & BIOMOLECULAR CHEMISTRY 6 23 4399 - 4405 2008年 [査読無し][通常論文]
   

  The optical rotation, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) of chiral sulfinates have been studied experimentally, and analysed by density functional theory calculation, aiming at establishing a reliable and convenient methodology to determine their absolute configuration. Through the study on a model chiral sulfinate with known absolute configuration, (R)-(+)-methyl p-toluenesulfinate ((R)-(+)-1), each technique was found to be reliable in assigning chirality of sulfinates. We then applied these methods to a synthetically prepared cruciferous phytoalexin, brassicanal C ((-)-2), and unambiguously determined its absolute configuration as S. The advantages and disadvantages of each spectroscopy on sulfinates are also discussed.
• Stereoselective synthesis of (R)-(+)-1-methoxyspirobrassinin, (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether and their enantiomers or diastereoisomers

  Zuzana C. Curillova, Peter Kutschy, Mariana Budovska, Atsufumi Nakahashi, Kenji Monde

  TETRAHEDRON LETTERS 48 46 8200 - 8204 2007年11月 [査読無し][通常論文]
   

  Stereoselective synthesis of cruciferous indole phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(-)-enantiomer was achieved by spirocyclization of 1-methoxybrassinin in the presence of (+)- and (-)-menthol and subsequent oxidation of the obtained menthyl ethers. Methanolysis of menthyl ethers in the presence of TFA afforded (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether as well its unnatural (2S,3S)-, (2R,3S)-, and (2S,3R)-isomers. (C) 2007 Elsevier Ltd. All rights reserved.
• Stereochemical studies of sialic acid derivatives by vibrational circular dichroism

  Atsufumi Nakahashi, Tohru Taniguchi, Nobuaki Miura, Kenji Monde

  ORGANIC LETTERS 9 23 4741 - 4744 2007年11月 [査読無し][通常論文]
   

  Systematic VCD studies of N-acetylneuraminic acid (Neu5Ac), a recognition-related unique carbohydrate, were performed for the first time. Two pairs of anomeric isomers regarding a quaternary C2 asymmetric carbon of Neu5Ac derivatives were synthesized. VCD spectral patterns around the ester carbonyl region, as well as other NOR regions, would be practical markers to distinguish the C2 stereochemistry.
• Spectrum−Structure Relationship in Carbohydrate Vibrational Circular Dichroism and Its Application to Glycoconjugates.

  Tohru Taniguchi, Kenji Monde

  Chem. Asian J. 2 10 1258 - 1266 2007年10月 [査読有り][通常論文]
   

  Preliminary reports of the nature of the vibrational circular dichroism (VCD) peak at around 1145 cm(-1), which is characteristic of axial glycosidic sugars and is called the glycoside band (J. Am. Chem. Soc. 2004, 126, 9496), have been throughly examined. Through systematic carbohydrate measurements, it was found that the sign of the glycoside band reflects not only the anomeric configuration but also the pyranose conformation. Isotope and theoretical studies characterized its vibrational mode as C1-H1 deformation coupled with C1-O1 stretching, which indicates its applicability to more-complicated glycoconjugates. In this study, for the first time, carbohydrate VCD spectra were reliably predicted by means of density functional theory (DFT) calculations. The VCD technique was applied to glycopeptides, and simultaneous analysis of both the carbohydrate and aglycan parts was carried out.
• "Effects of Central Metals Ions on Vibrational Circular Dichroism Spectra of Tris-(β-diketonato)Metal(III) Complexes"

  Hisako Sato, Tohru Taniguchi, Atsufumi Nakahashi, Kenji Monde, Akihiko Yamagishi

  Inorg. Chem. 46 16 6755 - 6766 2007年08月 [査読無し][通常論文]
   

  Vibrational circular dichroism (VCD) spectra of a series of [M(III)(acac)(3)] (acac = acetylacetonato; M = Cr, Co, Ru, Rh, Ir, and Al) and [M(III)(acac)(2)(dbm)] (dbm = dibenzoylmethanato; M = Cr, Co, and Ru) have been investigated experimentally and/or theoretically in order to see the effect of the central metal ion on the vibrational dynamics of ligands. The optical antipodes give the mirror-imaged spectra in the region of 1700-1000 cm(-1). The remarkable effect of the central metal ion is observed experimentally on the VCD peaks due to C-O stretches (1500-1300 cm(-1)) for both [M(III)(acac)(3)] and [M(III)(acac)(2)(dbm)]. In the case of Delta-[M(III)(acac)(3)], for example, the order of frequency of two C-O stretches (E and A(2) symmetries) is dependent on the kind of a central metal ion as follows: E (-) > A(2) (+) for M = Co, Rh, and Ir, while A(2) (+) > E (-) for M = Cr and Ru. In the case of Delta-[M(III)(acac)(2)(dbm)], the order of frequency of three C-O stretches (A, B, and B symmetries) is as follows: A (-) > B (+) > B (+) for Co(III), B (+) > A (-) > B (-) for Cr(III), and A (-) > B (+) > B (-) for Ru(III). These results imply that the energy levels of C-O stretches are delicately affected by the kind of central metal ion. Since such detailed information is not obtained from the IR spectra alone, the VCD spectrum can probe the effect of the central metal ion on interligand cooperative vibration modes.
• A structure and an absolute configuration of (+)-alternamin, a new coumarin from Murraya alternans having antidote activity against snake venom

  Hia Myoe Min, Mya Aye, Tohru Taniguchi, Nobuaki Miura, Kenji Monde, Kazuhiko Ohzawa, Toshiaki Nikai, Masatake Niwa, Yoshiaki Takaya

  TETRAHEDRON LETTERS 48 35 6155 - 6158 2007年08月 [査読有り][通常論文]
   

  (+)-Alternamin (1), a new dihydrofuranocoumarin, was isolated from the aerial parts of Murraya alternans (Kurz) Swinge. The analysis 2-D NMR correlation of (+)-1 led to either of linear dihydrofuranocoumarin (2A, 2C) or angular one (213). An IR and a vibrational circular dichroism (VCD) studies were conducted to distinguish the structure and to assign the absolute configuration. By comparison of the observed spectra with the calculated spectra for (S)-2A, (S)-2B, and (R)-2C, the molecular structure of (+)-1 was determined to be (S)-(+)-5,8-dimethoxymarmesin. The compound exhibited antidote activity against snake venom from Trimeresurus flavoviridis, affording experimental support for the pharmacological use of M. alternans. (c) 2007 Elsevier Ltd. All rights reserved.
• Effect of pore size on in vitro cartilage formation using chitosan-based hyaluronic acid hybrid polymer fibers

  Shintaro Yamane, Norimasa Iwasaki, Yasuhiko Kasahara, Kazuo Harada, Tokifumi Majima, Kenji Monde, Shin-ichiro Nishimura, Akio Minami

  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 81A 3 586 - 593 2007年06月 [査読無し][通常論文]
   

  In this study, we successfully developed three-dimensional scaffolds fabricated from the chitosan-based hyaluronic acid hybrid polymer fibers, which can control the porous structure. To determine the adequate pore size for enhancing the chondrogenesis of cultured cells, we compared the behaviors of rabbit chondrocytes in scaffolds comprising different pore sizes (100, 200, and 400 mu m pore size). Regarding the cell proliferation, there was no significant difference among the three groups. On the other hand, glycosaminoglycan contents in the 400 pm group significantly increased during the culture period, compared with those in the other groups. The ratio of type II to type I collagen mRNA level was also significantly higher in the 400 mu m group than in the other groups. These results indicate that our scaffold with 400 mu m pore size significantly enhances the extracellular matrix synthesis by chondrocytes. Additionally, the current scaffolds showed high mechanical properties, compared with liquid and gel materials. The data derived from this study suggest great promise for the future of a novel fabricated material with relatively large pore size as a scaffold for cartilage regeneration. The biological and mechanical advantages presented here will make it possible to apply our scaffold to relatively wide cartilaginous lesions. (C) 2006 Wiley Periodicals, Inc. J Biomed Mater Res 81A: 586-593, 2007.
• (R)-(+)-[VCD(+)9451-4-ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center

  Takuma Fujita, Kazuhiro Obataa, Shunsuke Kuwahara, Nobuaki Miura, Atsufumi Nakahashi, Kenji Monde, John Decatur, Nobuyuki Harada

  TETRAHEDRON LETTERS 48 24 4219 - 4222 2007年06月 [査読無し][通常論文]
   

  Enantiopure (R)-(+)-[VCD(+)945]-4-ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center, was synthesized by the use of M alpha NP acid method, and its absolute configuration was first unambiguously determined by the H-1 NMR anisotropy, X-ray crystallography, and VCD methods. (c) 2007 Elsevier Ltd. All rights reserved.
• Chiroptical analysis of glycoconjugates by vibrational circular dichroism (VCD)

  Taniguchi Tohru, Monde Kenji

  TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY 19 107 147 - 164 2007年05月 [査読有り][通常論文]
   

  This review describes theoretical and experimental aspects of vibrational circular dichroism (VCD) spectroscopy, and its application to structure analysis of carbohydrates targeting on their chiral property.
• Vibrational circular dichroism (VCD) studies on disaccharides in the CH region: toward discrimination of the glycosidic linkage position

  Tohru Taniguchi, Kenji Monde

  ORGANIC & BIOMOLECULAR CHEMISTRY 5 7 1104 - 1110 2007年 [査読無し][通常論文]
   

  The structural features of carbohydrates are a combination of 1) sequence and types of mono-sugars, 2) stereochemistry of their glycosidic linkages, and 3) their glycosidic linkage sites. We performed the first systematic VCD study on glycoside linking site discrimination. VCD spectra, in the CH stretching region from 2000 to 4000 cm(-1), of eleven glucobioses (trehalose (alpha 1-alpha 1), neotrehalose (alpha 1-beta 1), isotrehalose (beta 1-beta 1), kojibiose (alpha 1-2), nigerose (alpha 1-3), maltose (alpha 1-4), isomaltose (alpha 1-6), sophorose (beta 1-2), laminaribiose (beta 1-3), cellobiose (beta 1-4), gentiobiose (beta 1-6)) suggested a possible new discrimination method for glyco analysis, while VCD spectra in the mid-IR region distinguished the stereochemistry (alpha or beta) of the glycosidic linkage. Both reducing and nonreducing glucobioses showed different VCD spectral features compared to their constituent D-glucose and the anomer-fixed model compounds. Interresidue interaction such as hydrogen bonding was suggested to cause these spectral differences. Interplay between residues is a common phenomenon and thus VCD analysis could be applicable to other di-, oligo- or poly-saccharides. Several isotropic labeled compounds were also measured to support spectral assignment and interpretation.
• 赤外円二色性を用いた絶対配置決定 - 誘導化を必要としない溶液状態での絶対配置決定法

  門出健次, 三浦信明, 谷口透

  化学と生物 45 7 455 - 458 日本農芸化学会 2007年 [査読無し][通常論文]
  
• Rewinding of Helical Systems by Use of the Cr(III) Complex as a Photoresponsive Chiral Dopant

  Tohru Taniguchi, Kenji Monde, Shin-Ichiro Nishimura, Jun Yoshida, Hisako Sato, Akihiko Yamagishi

  Molecular Crystals and Liquid Crystals 460 1 107 - 116 2006年12月01日
• 赤外円二色性スペクトル : 紫外・可視発色団を必要としない新しいキラル分析法

  門出 健次

  高分子 55 7 516 - 519 The Society of Polymer Science, Japan 2006年07月01日
• Absolute configurations of endoperoxides determined by vibrational circular dichroism (VCD)

  Kenji Monde, Tohru Taniguchi, Nobuaki Miura, Charles S. Vairappan, Minoru Suzuki

  TETRAHEDRON LETTERS 47 26 4389 - 4392 2006年06月 [査読無し][通常論文]
   

  Diastercomeric mixture on the peroxide portion of ail endoperoxide acetylmajapolene A (1) was efficiently separated by HPLC on a chiral column, submitting to vibrational circular dichroism (VCD) investigation. The ab initio theoretical VCD and IR calculations of 1a and 1b were performed by density functional theory (DFT) using the B3PW91/6-31G(d.p) level of theory. Focusing on an isolated characteristic peroxide vibrational band, absolute configurations of 1a and 1b were unambiguously determined Lis (1R,4R,7S,10S) and (1S,4S,7S,10S), respectively. This is the first VCD application to endoperoxides which exist abundantly in nature. (c) 2006 Elsevier Ltd. All rights reserved.
• Absolute configurations of brominated sesquiterpenes determined by vibrational circular dichroism

  K Monde, T Taniguchi, N Miura, CS Vairappan, M Suzuki

  CHIRALITY 18 5 335 - 339 2006年05月 [査読無し][通常論文]
   

  Two brominated sesquiterpenes, majapolene B (1) and acetylmajapolene B (2), isolated from the red algal genus Laurencia were investigated using vibrational circular dichroism (VCD). The ab initio theoretical VCD and IR calculations of 1 and 2 were performed by density functional theory (DFT) using the B3PW91/631G(d,p) basis set. The experimental VCD spectra and corresponding population-weighted theoretical VCD spectra were found to be in excellent agreement in CCl4 solution in the 1800-850 cm(-1) region, which allowed unambiguous determination of the absolute configurations of (-)-1 and (-)-2 as 7S,10S and 7S,10S, respectively.
• Conformational analysis of chiral helical perfluoroalkyl chains by VCD

  Kenji Monde, Nobuaki Miura, Mai Hashimoto, Tohru Taniguchi, Tamotsu Inabe

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 18 6000 - 6001 2006年05月 [査読無し][通常論文]
  
• Dramatic effects of d-electron configurations on vibrational circular dichroism spectra of tris(acetylacetonato)metal(III)

  Hisako Sato, Tohru Taniguchi, Kenji Monde, Shin-Ichiro Nishimura, Akihiko Yamagishi

  CHEMISTRY LETTERS 35 4 364 - 365 2006年04月 [査読無し][通常論文]
   

  The VCD spectra of a series of tris(acetylacetonato)metal(III) ([M(acac)(3)] with M = Co, Cr, Ru, and Rh) have revealed a new aspect concerning the effects of a central metal ion on the vibrational energy levels split by the inter-ligand interactions. Our present view is that the correlated vibrational motions of vicinal ligands are affected by the d-electron configuration of a central metal ion.
• "A theoretical study of α- and β-D-glucopyranose conformations by the density functional theory"

  N Miura, T Taniguchi, K Monde, SI Nishimura

  Chem. Phys. Lett. 419 4-6 326 - 332 2006年02月 [査読無し][通常論文]
   

  A theoretical investigation of stable conformations Of D-glucopyranose was carried out using the density functional theory (DFT). Solvation effects were also evaluated with polarization continuum model (PCM) calculations. The 6-311++G(2d,2p) basis sets were appropriate. The estimated populations of gg, gt, and tg hydroxylmethyl rotamers were 53, 46, and 1 for alpha-(D)-glucopyranose and 48, 5 1, and I for beta-D-glucopyranose. Estimated ratios of alpha- to beta-anomers were 26 and 74, respectively. These populations are in good agreement with the NMR experiments. The first calculations of the vibrational circular dichroism (VCD) spectra Of D-glucopyranose were also performed. (c) 2005 Elsevier B.V. All rights reserved.
• High throughput quantitative glycomics and glycoform-focused proteomics of murine dermis and epidermis

  R Uematsu, J Furukawa, H Nakagawa, Y Shinohara, K Deguchi, K Monde, SI Nishimura

  MOLECULAR & CELLULAR PROTEOMICS 4 12 1977 - 1989 2005年12月 [査読無し][通常論文]
   

  Despite recent advances in our understanding of the significance of the protein glycosylation, the throughput of protein glycosylation analysis is still too low to be applied to the exhaustive glycoproteomic analysis. Aiming to elucidate the N-glycosylation of murine epidermis and dermis glycoproteins, here we used a novel approach for focused proteomics. A gross N-glycan profiling (glycomics) of epidermis and dermis was first elucidated both qualitatively and quantitatively upon N-glycan derivatization with novel, stable isotope-coded derivatization reagents followed by MALDI-TOF(/TOF) analysis. This analysis revealed distinct features of the N-glycosylation profile of epidermis and dermis for the first time. A high abundance of high mannose type oligosaccharides was found to be characteristic of murine epidermis glycoproteins. Based on this observation, we performed high mannose type glycoform-focused proteomics by direct tryptic digestion of protein mixtures and affinity enrichment. We identified 15 glycoproteins with 19 N-glycosylation sites that carry high mannose type glycans by off-line LC-MALDI-TOF/TOF mass spectrometry. Moreover the relative quantity of microheterogeneity of different glycoforms present at each N-glycan binding site was determined. Glycoproteins identified were often contained in lysosomes (e.g. cathepsin L and gamma-glutamyl hydrolase), lamellar granules (e.g. glucosylceramidase and cathepsin D), and desmosomes (e g. desmocollin 1, desmocollin 3, and desmoglein). Lamellar granules are organelles found in the terminally differentiating cells of keratinizing epithelia, and desmosomes are intercellular junctions in vertebrate epithelial cells, thus indicating that N-glycosylation of tissue-specific glycoproteins may contribute to increase the relative proportion of high mannose glycans. The striking roles of lysosomal enzymes in epidermis during lipid remodeling and desquamation may also reflect the observed high abundance of high mannose glycans.
• "Rational Design, Synthesis, and Characterization of Novel Inhibitors for Human β1,4- Galactosyltransferase"

  K Takaya, N Nagahori, M Kurogochi, T Furuike, N Miura, K Monde, YC Lee, SI Nishimura

  J. Med. Chem. 48 19 6054 - 6065 2005年09月 [査読無し][通常論文]
   

  An affinity labeling reagent, uridine 5'-(6-amino-{2-[(7-bromomethyl-2-naphthyl)methoxy-carbonylmethoxy]ethoxy}acetyl-6-deoxy-alpha-D-galactopyranosyl) diphosphate (1a), was designed on the basis of 3D docking simulation and synthesized to investigate the functional role of Trp310 residue located in the small loop near the active site of human recombinant galactosyltransferase (beta GalT-1). Mass spectrometric analysis revealed that the Trp310 residue of beta GalT1 can be selectively modified with the naphthylmethyl group of compound la at the C-3 position of the indole ring. This result motivated us to synthesize novel uridine-5'-diphosphogalactose (UDP-Gal) analogues as candidates for mechanism-based inhibitors for beta GalT-1. We found that uridine 5'-(6-O-[10-(2-naphthyl)-3,6,9-trioxadecanyl]-alpha-D-galactopyranosyl) diphosphate (2) is the strongest inhibitor (K-i = 1.86 mu M) against UDP-Gal (K-m = 4.91 mu M) among compounds reported previously. A cold spray ionization time-of-flight mass spectrometry study demonstrated that the complex of this inhibitor and beta GalT-1 cannot interact with an acceptor substrate in the presence of Mn2+.
• Chiral cruciferous phytoalexins: Preparation, absolute configuration, and biological activity

  K Monde, T Taniguchi, N Miura, P Kutschy, Z Curillova, M Pilatova, J Mojzis

  BIOORGANIC & MEDICINAL CHEMISTRY 13 17 5206 - 5212 2005年09月 [査読有り][通常論文]
   

  Synthesized by an efficient one-pot spirocyclization method, two chiral cruciferous phytoalexins, 1-methoxyspirobrassinin (2) and 1-methoxyspirobrassinol methyl ether (4a), were prepared through optical resolution using the chiral HPLC method of corresponding racemates. The absolute configuration of natural (+)-2 was elucidated as R by using the direct comparison of ECD and VCD spectra with those of known (S)-(-)-spirobrassinin (1). Another chiral phytoalexin, (-)-4a, had its absolute configuration 2R,3R elucidated through the comparison of observed and calculated VCD. Interestingly, the absolute configurations of natural (S)(-)-spirobrassinin (1) and (R)-(+)-1-methoxyspirobrassinin (2) were opposite of each other, even though their structures are almost similar, with the exception of an N-methoxy group. A significant difference in the antiproliferative activity between (2R,3R)-(-) and (2S,3S)-(+)-4a was observed. (c) 2005 Elsevier Ltd. All rights reserved.
• Versatile glycoblotting nanoparticles for high-throughput protein glycomics

  K Niikura, R Kamitani, M Kurogochi, R Uematsu, Y Shinohara, H Nakagawa, K Deguchi, K Monde, H Kondo, SI Nishimura

  CHEMISTRY-A EUROPEAN JOURNAL 11 13 3825 - 3834 2005年06月 [査読無し][通常論文]
   

  We have developed an effective and practical trap-and-release method based on chemoselective ligation of carbohydrates with reactive aminooxyl groups attached to the surface of nanoparticles (referred to as glycoblotting nanoparticles). These glycoblotting nanoparticles were synthesized by UV irradiation of diacetylene-functionalized lipids that contain the aminooxyl group. The glycoblotting nanoparticles captured carbohydrates in aqueous solution under mild conditions and were collected by simple centrifugation. ne trapped carbohydrates were effectively released from the nanoparticles under acidic conditions to give pure oligosaccharides. This glycoblotting process reduced the time required for the purification process of carbohydrates to less than 6 h, compared to the several days needed for conventional chromatographic techniques. The oligosaccharides (N-glycan) were released from ovalbumin (glyco-protein) by PNGaseF after tryptic digestion. MALDI-TOF mass spectra before purification did not show any significant signals corresponding to N-glycans because these signals were hidden by the large signals of the abundant peptides. However, after purification with the glycoblotting nanoparticles, only signals corresponding to oligosaccharides appeared. We also demonstrated a clear analysis of the oligosaccharides contained in the mice dermis by means of glycoblotting.
• Cruciferous phytoalexins: antiproliferative effects in T-Jurkat leukemic cells

  M Pilatova, M Sarissky, P Kutschy, A Mirossay, R Mezencev, Z Curillova, M Suchy, K Monde, L Mirossay, J Mojzis

  LEUKEMIA RESEARCH 29 4 415 - 421 2005年04月 [査読無し][通常論文]
   

  We tested antiproliferative activity of selected cruciferous phytoalexins including brassinin, 1-methoxybrassinin, (+/-)-spirobrassin, (+/-)1-methoxyspirobrassinin and (+/-)-1-methoxyspirobrassinol, in leukemic Jurkat cell. The most effective of the tested phytoalexins was Imethoxybrassinin with IC50 10 mu mol 1(-1). However, significant effect of all phytoalexines was also determined at concentration 1 mu mol 1(-1). In 1-methoxybrassinin-treated Jurkat cells, we found significant increase in the fraction of cells with a sub-G(0)/G(1) DNA content, which is considered to be a marker of cell death by apoptosis. Apoptosis was also confirmed by the annexin V staining. In summary, 1-methoxybrassinin exerted potent antiproliferative activity probably due to cell cycle arrest and apoptosis induction. (c) 2004 Elsevier Ltd. All rights reserved.
• Antihyperglycaemic flavonoids from Syzygium samarangense (Blume) Merr. and Perry

  MHC Resurreccion-Magno, IM Villasenor, N Harada, K Monde

  PHYTOTHERAPY RESEARCH 19 3 246 - 251 2005年03月 [査読無し][通常論文]
   

  2',4'-Dihydroxy-3',5'-dimethyl-6'-methoxychalcone 1, its isomeric flavanone 5-O-methyl-4'-desmethoxymatteucinol 2 and 2'4'-dihydroxy-6'-methoxy-3'-methylchalcone 3 were isolated from the leaves of S. samarangense using a bioassay-directed scheme. In an oral glucose tolerance test, at a dosage of 1.0 mg/20 g mouse, 1 and 2 significantly (alpha = 0.05) lowered the blood glucose levels (BGLs) in glucose-hyperglycaemic mice when administered 15 min after a glucose load. When co-administered with glucose, only 1 showed a significant lowering of BGLs 45 min after its oral administration. When administered 15 min before glucose, none of the flavonoids showed a positive effect. Only 1 decreased significantly, at alpha = 0.05, the BGLs of alloxan-diabetic mice at t = 90-150 min. Copyright (c) 2005 John Wiley & Sons, Ltd.
• Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering

  S Yamane, N Iwasaki, T Majima, T Funakoshi, T Masuko, K Harada, A Minami, K Monde, S Nishimura

  BIOMATERIALS 26 6 611 - 619 2005年02月 [査読無し][通常論文]
   

  In this study, we hypothesized that hyaluronic acid could provide superior biological effects on the chondrocytes in a three-dimensional culture system. To test this hypothesis, we investigated the in vitro behavior of rabbit chondrocytes oil a novel chitosan-based hyaluronic acid hybrid polymer fiber. The goal of the current study was to show the Superiority of this novel fiber as a scaffold biomaterial for cartilage tissue engineering. Chitosan polymer fibers (chitosan group) and chitosan-based hyaluronic acid hybrid polymer fibers (HA 0.04% and HA 0.07% groups, chitosan coated with hyaluronic acid 0.04% and 0.07%, respectively) were originally developed by the wetspinning method. Articular chondrocytes were isolated from Japanese white rabbits and cultured in the sheets consisting of each polymer fiber. The effects of each polymer fiber oil cell adhesivity, proliferation, morphological changes. and synthesis of the extracellular matrix were analyzed by quantitative a cell attachment test, DNA quantification, light and scanning electron microscopy, semi-quantitative RT-PCR, and immunohistochemical analysis. Cell adhesivity, proliferation and the synthesis of agrecan were significantly higher in the hybrid fiber (HA 0.04% and 0.07%) groups than in the chitosan group. On the cultured hybrid polymer materials, scanning electron microscopic observation showed that chondrocytes proliferated while maintaining their morphological phenotype and with a rich extracellular matrix synthesis around the cells. Immunohistochemical staining with an anti-type II collagen antibody demonstrated rich production of the type II collagen in the pericellular matrix from the chondrocytes. The chitosan-based hyaluronic acid hybrid polymer fibers show great potential as a desirable biomaterial for cartilaginous tissue scaffolds. (C) 2004 Elsevier Ltd. All rights reserved.
• "Chemical and Enzymatic Synthesis of Glycocluster Having Seven Sialyl Lewis X Arrays Using β-Cyclodextrin as a Key Scaffold Material"

  T Furuike, R Sadamoto, K Niikura, K Monde, N Sakairi, SI Nishimura

  Tetrahedron 61 7 1737 - 1742 2005年02月 [査読無し][通常論文]
   

  An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from beta-cyclodextrin (beta-CD) as a key starting scaffold material. A key intermediate, beta-CD derivative having seven N-acetyl-D-glucosamine (GlcNAc) residues [(GlcNAc)(7)CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-beta-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)(7)CD proceeded smoothly by means of beta-1,4-galactosyltransferase, alpha-2,3-sialyltransferase, and alpha-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (M-w = 7924.5, calcd for C301H490N21O196S7Na7; MALDI-TOF MS, m/z 7946 [M + Na](+)) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)(7)CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method. (C) 2004 Elsevier Ltd. All rights reserved.
• High-throughput protein glycomics: Combined use of chemoselective glycoblotting and MALDI-TOF/TOF mass spectrometry

  SI Nishimura, K Niikura, M Kurogochi, T Matsushita, M Fumoto, H Hinou, R Kamitani, H Nakagawa, K Deguchi, N Miura, K Monde, H Kondo

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 1 91 - 96 2005年 [査読無し][通常論文]
  
• Direct observation of sugar-protein, sugar-sugar, and sugar-water complexes by cold-spray ionization time-of-flight mass spectrometry

  SI Nishimura, N Nagahori, K Takaya, Y Tachibana, N Miura, K Monde

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 4 571 - 575 2005年 [査読無し][通常論文]
  
• Versatile synthesis of oligosaccharide-containing fullerenes

  S Abe, H Moriyama, K Niikura, F Fei, K Monde, S Nishimura

  TETRAHEDRON-ASYMMETRY 16 1 15 - 19 2005年01月 [査読無し][通常論文]
   

  Oxylamine-functionalized fullerene derivatives have been synthesized in order to attach oligosaccharides to the fullerene surface by simple chemical ligation. This method greatly simplifies the synthetic process for a variety Of oligosaccharide-containing fullerenes without any complicated chemical modification. (C) 2004 Elsevier Ltd. All rights reserved.
• Assignment and quantification of 2-aminopyridine derivatized oligosaccharide isomers coeluted on reversed-phase HPLC/MS by MSn spectral library

  Y Takegawa, K Deguchi, S Ito, S Yoshioka, A Sano, K Yoshinari, K Kobayashi, H Nakagawa, K Monde, SI Nishimura

  ANALYTICAL CHEMISTRY 76 24 7294 - 7303 2004年12月 [査読無し][通常論文]
   

  2-Aminopyridine (PA)-derivatized oligosaccharides from IgG were analyzed by using reversed-phase HPLC/mass spectrometry (RP-HPLC/MS) and a MSn spectral library, in particular, focusing on two pairs of isomers incompletely separated or coeluted in chromatograms. We previously reported that MSn spectral matching considering both major fragment ions (m/z) and intensities is useful and applicable to the structural assignment of PA-oligosaccharide isomers. In this study, MSn spectral matching based on the MSn spectral library was applied to the assignment of these PA-oligosaccharide isomers in IgG. Its usefulness was investigated by comparing it to the conventional two-dimensional mapping method based on retention time indexes. Specifically, we focus on the assignment and quantification of the isomers, which are coeluted in chromatograms. From this, we propose a new method using MSn spectral matching and the working curve on which are plotted the relative intensities of selected fragment ions in their MS2 spectra versus various mixtures of the isomers. This new method demonstrated that the obtained quantities coincide very well with those estimated after separating by a combination of lectin and reversed-phase columns. This means that separation by RP-HPLC/MS is greatly simplified because complete separation of the isomers is no longer required. Application of this new method was tested by using the two other pairs of fucosylated and nonfucosylated PA-oligosaccharides from IgG. The results showed that this method works for them as well.
• Glycoinsulins: Dendritic sialyloligosaccharide-displaying insulins showing a prolonged blood-sugar-lowering activity

  Masaaki Sato, Tetsuya Furuike, Reiko Sadamoto, Naoki Fujitani, Taku Nakahara, Kenichi Niikura, Kenji Monde, Hirosato Kondo, Shin-Ichiro Nishimura

  Journal of the American Chemical Society 126 43 14013 - 14022 2004年11月03日 [査読無し][通常論文]
   

  Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by α2,6-sialyltransferase (α2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
• A characteristic CH band in VCD of methyl glycosidic carbohydrates

  T Taniguchi, K Monde, N Miura, S Nishimura

  TETRAHEDRON LETTERS 45 46 8451 - 8453 2004年11月 [査読無し][通常論文]
   

  Novel vibrational circular dichroism (VCD) studies in the CH region of a series of methyl glycosidic carbohydrates were examined. The specific CH stretching VCD band predicts absolute stereochemistries of their anomeric positions. The C-1 chiral information was extracted to the methoxy substituent as a probe. The concept of the vibrational chirality probe from a single chiral center in the presence of numerous such centers might be useful in determining the absolute configuration, when a multiplicity of chiral centers is present in a molecule such as a carbohydrate. (C) 2004 Elsevier Ltd. All rights reserved.
• Glycoinsulins: Dendritic sialyloligosaccharide-displaying insulins showing a prolonged blood-sugar-lowering activity

  M Sato, T Furuike, R Sadamoto, N Fujitani, T Nakahara, K Niikura, K Monde, H Kondo, SI Nishimura

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 43 14013 - 14022 2004年11月 [査読有り][通常論文]
   

  Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by alpha2,6-sialyltransferase (alpha2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-lns(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
• Sequential glycoproteins: Practical method for the synthesis of antifreeze glycoprotein models containing base labile groups

  Y Tachibana, K Monde, SI Nishimura

  MACROMOLECULES 37 18 6771 - 6779 2004年09月 [査読無し][通常論文]
   

  Practical and versatile methods for the preparation of glycopeptide polymers containing base labile moieties were established by use of 1-isobuthoxycarbonyl-2-isobuthoxy-1,2-dihydroquinoline (IIDQ) or 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as polycondensation agents of glycopeptide units without any protection on the carbohydrate residues. These methods were applied for the synthesis of mucin-like glycoprotein mimics related to antifreeze glycoproteins (AFGPs), giving the target O-acetylated glycopolypeptides efficiently, while the conventional DPPA (diphenylphosphoryl azide) method gave complex mixtures of acyl migrated compounds.
• Specific Band Observed in VCD Predicts the Anomeric Configuration of Carbohydrates

  K Monde, T Taniguchi, N Miura, SI Nishimura

  J. Am. Chem. Soc. 126 31 9496 - 9497 2004年08月 [査読有り][通常論文]
  
• Synthesis of 4-fluorinated UDP-MurNAc pentapeptide as an inhibitor of bacterial growth

  T Ueda, F Feng, R Sadamoto, K Niikura, K Monde, SI Nishimura

  ORGANIC LETTERS 6 11 1753 - 1756 2004年05月 [査読無し][通常論文]
   

  4-Fluorinated UDP-MurNAc pentapeptide, 2, has been synthesized. In our previous study, UDP-MurNAc pentapeptide analogue 1 was found to be incorporated into the bacterial cell wall through biosynthesis. Compound 2 showed growth-inhibition activity against Gram-positive bacteria when it was added to growth media at 0.01 mg/mL.
• Feasibility of polysaccharide hybrid materials for scaffolds in cartilage tissue engineering: Evaluation of chondrocyte adhesion to polyion complex fibers prepared from alginate and chitosan

  N Iwasaki, ST Yamane, T Majima, Y Kasahara, A Minami, K Harada, S Nonaka, N Maekawa, H Tamura, S Tokura, M Shiono, K Monde, SI Nishimura

  BIOMACROMOLECULES 5 3 828 - 833 2004年05月 [査読無し][通常論文]
   

  The ideal cell-carrier material for cartilage regeneration should be one that closely mimics the natural environment in a living articular cartilage matrix. In the current study, we considered that alginate-based chitosan hybrid biomaterials could provide excellent supports for chondrocyte adhesion. To test this hypothesis, we investigated the adhesion behavior of rabbit chondrocytes onto an alginate polymer versus the adhesion of the chondrocytes onto some alginate-based chitosan hybrid polymer fibers in vitro. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with chondrocytes in comparison with alginate polymer fiber. Additionally, morphologic studies revealed maintenance of the characteristic round morphology of the chondrocyte and the dense fiber of the type II collagen produced by the chondrocytes in the hybrid polymer. On the basis of these results, we conclude that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial for cartilage tissue scaffolds.
• Control of bacteria adhesion by cell-wall engineering

  R Sadamoto, K Niikura, T Ueda, K Monde, N Fukuhara, SI Nishimura

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 12 3755 - 3761 2004年03月 [査読無し][通常論文]
   

  UDP-MurNAc-pentapeptide derivative bacterial cell-wall precursors were synthesized as effective tools for surface display on living bacteria. Lactobacilli were incubated in the ketone-modified precursor-containing medium, and the ketone moiety was displayed on the bacterial surface through cell-wall biosynthesis. Oligomannose was coupled with the ketone moiety on the bacterial surface via a aminooxyl linker, thereby displaying this oligosaccharide on the surface of the bacteria. The increase in the adhesion of the sugar-displaying bacteria onto a concanavalin A-attached film compared to that of native bacteria was confirmed by microscopic observation and surface plasmon resonance measurement. The incorporation of the artificial cell-wall precursors was enhanced when incubated with fosfomycin, an inhibitor of cell-wall precursor biosynthesis.
• An engineered hyaluronan synthase - Characterization of recombinant human hyaluronan synthase 2 expressed in Escherichia coli

  H Hoshi, H Nakagawa, S Nishiguchi, K Iwata, K Niikura, K Monde, SI Nishimura

  JOURNAL OF BIOLOGICAL CHEMISTRY 279 4 2341 - 2349 2004年01月 [査読無し][通常論文]
   

  The Class I hyaluronan synthase ( HAS) is a unique glycosyltransferase synthesizing hyaluronan ( HA), a polysaccharide composed of GlcUA and GlcNAc, by using one catalytic domain that elongates two different monosaccharides. As for the synthetic mechanism, there are two alternative manners for the sugar elongation process. Some bacterial HASs add new sugars to the non-reducing end of the acceptor to grow polymers. On the other hand, some vertebrate enzymes seem to transfer sugars to the reducing end. Expression of vertebrate HASs as active and soluble proteins will accelerate further precise insight into mechanisms of sugar elongation reactions by natural HASs. Since large scale production of HA polymers and oligomers would become powerful tools both for basic studies and new biotechnology to create functional carbohydrates in medicinal purposes, advent of an efficient method for the expression of HASs in Escherichia coli is strongly expected. Here we communicate the first success of the production of recombinant human HAS2 proteins composed of only the catalytic region in E. coli as the active form. It was demonstrated that an engineered HAS2 expressed in E. coli exhibited significant activity to synthesize a mixture of HAS oligomers from 8-mer (HA8) to 16-mer (HA16). Engineered HAS2 prepared herein elongated sugars from exogenous tetrasaccharide to form polymers with a direction to the non-reducing end. According to the present results, large scale production of engineered recombinant HASs is to be performed using E. coli that will provide practical and economic advantages in manufacturing enzymes for use in the synthesis of various oligomeric HA molecules and their industrial applications.
• Antifreeze glycoproteins: Elucidation of the structural motifs that are essential for antifreeze activity

  Y Tachibana, GL Fletcher, N Fujitani, S Tsuda, K Monde, SI Nishimura

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 7 856 - 862 2004年 [査読無し][通常論文]
  
• Site-specific introduction of sialic acid into insulin

  M Sato, R Sadamoto, K Niikura, K Monde, H Kondo, SI Nishimura

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 12 1516 - 1520 2004年 [査読無し][通常論文]
  
• Structural assignment of isomeric 2-aminopyridine-derivatized oligosaccharides using MSn spectral matching

  Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 18 4 385 - 391 2004年 [査読無し][通常論文]
   

  Two isomeric pairs of 2-aminopyridine (PA)-derivatized fucosylated and non-fucosylated oligosaccharides (complex-type N-glycans of IgG) were analyzed using liquid chromatography/ion trap mass spectrometry (LC/ITMS) with a sonic spray ionization source and by varying the collision-induced dissociation voltage. Reproducibility of MSn (n = 2) spectra obtained by LC/ITMS was tested considering both fragment ions (m/z) and intensities. A comparison of their MSn spectra and evaluation of similarities (or matching), based on correlation coefficients between MSn spectra, was investigated as a possibility for structural assignment of the isomers. It is shown that such MSn spectral matching is useful and applicable to the structural assignment of relatively large fucosylated and sialylated PA-oligosaccharides released from IgG based on Bn- and Yn-type fragmentations of the corresponding [M+H+Na](2+) ions. Copyright (C) 2004 John Wiley Sons, Ltd.
• Fluorescent glyconanoparticles as a sensitive device to monitor sugar-involving molecular events

  K Niikura, N Osuga, N Nagahori, R Sadamoto, M Shiono, N Iwasaki, K Monde, A Minami, SI Nishimura

  POLYMER JOURNAL 36 3 209 - 218 2004年 [査読無し][通常論文]
   

  We prepared sugar-displayed fluorescent nanoparticles using photopolyinerization of the vesicles of diacetylene-containing glycolipids. After photopolymerization, the nanoparticles exhibited fluorescent emission at 400-600 nm upon excitation at 380 nm. The binding of sugar-recognizing proteins (lectins) onto the fluorecent nanoparticles induced changes in fluorescence. The fluorescent intensity of the nanoparticles decreased with an increase in lectin concentration. On the contrary, the enzymatic release of oligosaccharides from the glyconanoparticles gave an increase in fluorescence. Using a phosphatidylcholine-type lipid as the matrix lipid of the nanoparticles, the non-specific adsorption of lectins on the surface was drastically restricted, leading to the generation of a specific response to the target proteins.
• Chemo-enzymatic synthesis of fluorinated 2-N-acetamidosugar nucleotides using UDP-GlcNAc pyrophosphorylase

  F Feng, K Okuyama, K Niikura, T Ohta, R Sadamoto, K Monde, T Noguchi, SI Nishimura

  ORGANIC & BIOMOLECULAR CHEMISTRY 2 11 1617 - 1623 2004年 [査読無し][通常論文]
   

  Two non-natural. uorinated 2-N-acetamidosugar nucleotides, uridine 5'-diphosphate (UDP) 2-acetamido-2,4-dideoxy-4-fluoro-alpha-D-glucopyranose (UDP-4-FGlcNAc) 1 and its galacto isomer (UDP-4-FGalNAc) 2, were enzymatically constructed by treating chemically synthesized. uorinated 2-N-acetamidosugar 1-phosphates as the donor with UDP 2-acetamido-2-deoxy-alpha-D-glucopyranose pyrophosphorylase in the presence of uridine 5'-triphosphate (UTP).
• Artificial golgi apparatus: Direct monitoring of glycosylation reactions on automated glycosynthesizer

  SI Nishimura, N Nagahori, R Sadamoto, K Monde, K Niikura

  SYNTHESIS OF CARBOHYDRATES THROUGH BIOTECHNOLOGY 873 113 - 124 2004年 [査読有り][通常論文]
   

  Enzymatic synthesis is potential method for the construction of glycoconjugates as well as conventional chemical synthesis. Use of glycosyltransferases in the synthetic schemes has accelerated practical synthesis of oligosaccharides and related compounds. However, there is no systematic approach for establishing "automated glycosynthesizer" based on the combined chemical and enzymatic strategy. We have found that water-soluble glycopolymers bearing multivalent sugars become excellent glycosyl acceptor substrates of glycosyltransferases. Affinity of enzymes with multivalent glycosyl acceptors was drastically enhanced by polymeric sugar-cluster effect. Some designed linkers that can be recognized by specific enzyme permitted release of products from polymer supports under mild and selective conditions. By employing these water-soluble primers with some engineered glycosyltransferases, we succeeded to produce "artificial Golgi apparatus", an automatic glycosynthesizer controlled by computer. In this chapter, our recent approach for direct monitoring of sugar -elongation reactions by using surface plasmon resonance (SPR) method will be described, since direct and real time monitoring of enzymatic carbohydrate synthesis is strongly required for materializing practically usable artificial Golgi apparatus. (C) 2004 American Chemical Society.
• Preparation of cruciferous phytoalexin related metabolites, (-)-dioxibrassinin and (-)-3-cyanomethyl-3-hydroxyoxindole, and determination of their absolute configurations by vibrational circular dichroism (VCD)

  K Monde, T Taniguchi, N Miura, SI Nishimura, N Harada, RK Dukor, LA Nafie

  TETRAHEDRON LETTERS 44 32 6017 - 6020 2003年08月 [査読無し][通常論文]
   

  Cruciferous phytoalexin related metabolites, (-)-dioxibrassinin (1) and (-)-3-cyanomethyl-3-hydroxyoxindole (2) were prepared from isatin as racemates and were resolved by chiral HPLC. Their absolute configurations were determined by the new chiroptical technique, vibrational circular dichroism (VCD), as well as by the conventional electronic circular dichroism (ECD). It is concluded that the absolute configurations of the naturally occurring (-)-1 and (-)-2 are both S. (C) 2003 Elsevier Ltd. All rights reserved.
• Glycosyltransferase microarray displayed on the glycolipid LB membrane

  N Nagahori, K Niikura, R Sadamoto, M Taniguchi, A Yamagishi, K Monde, SI Nishimura

  ADVANCED SYNTHESIS & CATALYSIS 345 6-7 729 - 734 2003年06月 [査読無し][通常論文]
   

  beta(1-->4) Galactosyltransferase expressed as a fusion protein with maltose binding protein (MBP-GalT) was displayed specifically on a Langmuir-Blodgett (LB) membrane prepared by photopolymerization of maltotriose-carrying glycolipid (1) with 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (2). The catalytic activity of MBP-GalT on the LB film was directly monitored by the surface plasmon resonance (SPR) method using a GlcNAc-carrying water-soluble polymer (3) as an acceptor substrate. Highly sensitive sigmoidal-type signals were obtained upon the addition of the acceptor substrate in the presence of the donor substrate, UDP-galactose (UDP-Gal), while the binding of 3 was not detected in the absence of UDP-Gal. The intensities of the signals were dependent on the amount of immobilized MBP-GalT on the LB film, which was estimated from the images obtained by atomic force microscope (AFM).
• An efficient synthesis of a biantennary sialooligosaccharide analog using a 1,6-anhydro-beta-lactose derivative as a key synthetic block

  T Furuike, K Yamada, T Ohta, K Monde, SI Nishimura

  TETRAHEDRON 59 27 5105 - 5113 2003年06月 [査読無し][通常論文]
   

  An efficient and versatile method for the synthesis of a biantennary octasaccharide derivative was established by combined chemical and enzymatic manipulations of 1,6-anhydro-beta-lactose as a key starting material. A key 1,6-anhydro-beta-lactose derivative having two unprotected hydroxyl groups at C-3' and C-6' positions was prepared and employed for the chemical coupling reaction with a known 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl imidate to afford a tetrasaccharide derivative with two GlcNAc branches in 69% yield. Enzymatic galactosylation using UDP-Gal with a bovine milk beta1,4-galactosyltransferase and subsequent sialylation with a recombinant alpha,2,3-sialyltransferase in the presence of CMP-Neu5Ac proceeded smoothly and gave a desired model compound, a bivalent sialooctasaccharide (1), in 73% overall yield from the tetrasaccharide intermediate. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Synthesis of photopolymerizable glycolipids and their application as scaffolds to immobilize proteins with a micron-sized pattern

  N Nagahori, K Niikura, R Sadamoto, K Monde, SI Nishimura

  AUSTRALIAN JOURNAL OF CHEMISTRY 56 6 567 - 576 2003年 [査読無し][通常論文]
   

  Photopolymerizable glycolipids incorporating ceramide- or amido-type linkers and able to form stable monolayers were efficiently synthesized by chemical and enzymatic methods. Glycolipid polymer films served as platforms for the immobilization of proteins through specific carbohydrate - protein interactions at the air - water interface. Carbohydrate-binding proteins deposited on the glycolipid film were observed by atomic force microscopy, which showed varying submicron-sized protein patterns such as dendrites, dots, and networks, depending on the lipid structure, membrane preparation process, and sugar density of the membrane. Surface plasmon resonance measurement confirmed that the subunit-type lectins immobilized on the glycolipid membranes exhibited the ability to interact specifically with carbohydrate ligands by using unoccupied binding sites.
• Glycotentacles: Synthesis of cyclic glycopeptides, toward a tailored blocker of influenza virus hemagglutinin

  T Ohta, N Miura, N Fujitani, F Nakajima, K Niikura, R Sadamoto, CT Guo, T Suzuki, Y Suzuki, K Monde, SI Nishimura

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 42 42 5186 - 5189 2003年 [査読無し][通常論文]
  
• Cell wall engineering of living bacteria through biosynthesis.

  Sadamoto R, Niikura K, Monde K, Nishimura S

  Methods in enzymology 362 273 - 286 2003年 [査読有り][通常論文]
  
• Efficient and versatile synthesis of mucin-like glycoprotein mimics

  Y Tachibana, N Matsubara, F Nakajima, T Tsuda, S Tsuda, K Monde, SI Nishimura

  TETRAHEDRON 58 51 10213 - 10224 2002年12月 [査読無し][通常論文]
   

  An efficient synthetic method of sequential glycopeptide-polymer by means of the combined chemical and enzymatic strategy was applied to the practical synthesis of some tandem repeating mucin-type glycoproteins. Versatility of the present synthetic strategy was demonstrated by elucidating some physicochemical and conformational analyses of these synthetic mucins. (C) 2002 Elsevier Science Ltd. All rights reserved.
• "Spirocyclization strategy toward indole phytoalexins. The first synthesis of (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, and (±)-1-methoxyspirobrassinol methyl ether"

  P Kutschy, M Suchy, K Monde, N Harada, R Maruskova, Z Curillova, M Dzurilla, M Miklosova, R Mezencev, J Mojzis

  Tetrahedron Lett. 43 52 9489 - 9492 2002年12月 [査読無し][通常論文]
   

  The first syntheses of cruciferous indole phytoalexins (+/-)-1-methoxyspirobrassinin, (+/-)-1-methoxyspirobrassinol, (+/-)-1-methoxyspirobrassinol methyl ether as well as a new syntheses of phytoalexins (+/-)-spirobrassinin and cyclobrassinin were achieved by dioxane dibromide (DDB)-mediated spirocyclization of brassinin and its I-substituted derivatives. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Cell-wall engineering of living bacteria

  R Sadamoto, K Niikura, PS Sears, HT Liu, CH Wong, A Suksomcheep, F Tomita, K Monde, SI Nishimura

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 124 31 9018 - 9019 2002年08月 [査読無し][通常論文]
  
• Absolute stereochemistry of chiral C-60 fullerene bis-adducts

  K Yoshida, S Osawa, K Monde, M Watanabe, N Harada

  ENANTIOMER 7 1 23 - 32 2002年01月 [査読無し][通常論文]
   

  To determine the absolute configuration of chiral fullerene bis-adducts, we have studied the double Bingel reaction of C-60 with chiral tether (2S,3S)-(-)-9 derived from (R,R)-(+)-tartaric acid, and have succeeded in isolating two possible chiral bis-adducts 10a (5%) and 10b (2%) in addition to the C-s-symmetrically added derivative 10c (40%). The CD spectra of chiral bis-adducts [CD(+)281]-10a and [CD(-)281]-10b show very intense Cotton effects, which are almost of mirror image, indicating that their chiral C-60 pi-electron systems are enantiomeric each other. The H-1 and C-13 NMR spectra of 10a and 10b indicate that they have C-2-symmetrical structures, and the vicinal coupling constants between two equivalent protons H-2 and H-2' were determined as 1.2 Hz for 10a and 1.8 Hz for 10b, respectively by the 13 C satellite band method. From the conformational analyses, the absolute configurations of these chiral C60 fullerene bis-adducts were unambiguously determined as [CD(+)281]-(S,S,C-f)-10a and [CD(-)281]-(S,S,(f)A)-10b, respectively.
• Erythrocyte-like liposomes prepared by means of amphiphilic cyclodextrin sulfates

  T Sukegawa, T Furuike, K Niikura, A Yamagishi, K Monde, SI Nishimura

  CHEMICAL COMMUNICATIONS 430 5 430 - 431 2002年 [査読無し][通常論文]
   

  A novel class of sulfated glycolipids with excellent self-assembling capacity to form stable monolayers at an air-water interface and specific erythrocyte-like liposomes was synthesised from alpha, beta, and gamma-cyclodextrins as starting materials.
• Measurement of interfluorine distances in solids

  ML Gilchrist, K Monde, Y Tomita, T Iwashita, K Nakanishi, AE McDermott

  JOURNAL OF MAGNETIC RESONANCE 152 1 1 - 6 2001年09月 [査読無し][通常論文]
   

  F-19 homonuclear dipolar recoupling methods were used to measure internuclear distances ranging from 5 to 12 Angstrom in fluorinated organic compounds in the solid state. Magic-angle-spinning-based high-resolution techniques were utilized. Trifluoromethyl and aromatic fluorine groups were seperated by rigid aromatic spacers; these compounds were diluted into nonfluorinated host molecule matrices to give isolated homonuclear spin pairs with known internuclear distances. Radiofrequency-driven recoupling (RFDR) was used to elicit magnetization exchange between the spin pairs in 1D and 2D experiments. Simulation of the exchange was accomplished using a Monte Carlo-type algorithm to search the parameter space. These methods allow the determination of distances with an accuracy of 1 Angstrom at shorter distances and 2 Angstrom at longer distances, with the assumption of no prior knowledge of T-2(ZQ). (C) 2001 Academic Press.
• Synthesis, absolute configuration, and enantiomeric enrichment of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin, and its oxazoline analog

  M Suchy, P Kutschy, K Monde, H Goto, N Harada, M Takasugi, M Dzurilla, E Balentova

  JOURNAL OF ORGANIC CHEMISTRY 66 11 3940 - 3947 2001年06月 [査読無し][通常論文]
   

  Stereochemical studies of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin [(-)-4], and its oxazoline analogue, spirooxazoline (11), were carried out. Racemic spirobrassinin [(+/-)-4] was synthesized by SOCl2- or MsCl-mediated cyclization of dioxibrassinin [(+/-)-8], Treatment of ( 3-hydroxyoxindol-3-yl)methylammonium chloride [(+/-)-9] with CSCl2 and subsequent methylation of the obtained spirooxazolidinethione (+/-)-10 afforded spirooxazoline [(+/- )11]. Enantioresolution of (+/-)-4 and (+/- )11 was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate (12), chromatographic separation of diastereomeric amides 13, 14 or 15, 18, and their cleavage with CH3ONa. Absolute configuration of the stereogenic center in natural (S)-(-)-4 was derived from the exciton, calculated via CD methods, and unequivocally confirmed by X-ray crystallographic analyses of 1-[1 'S,4 'R-(-)-camphanoyl] derivatives [(-)-19 and (-)-20] of (+/-)- and (-)-4. Novel enantiomeric enrichment phenomena of 4 and 11 were discovered during their chromatographic separations under achiral HPLC conditions. Screening of antifungal activity against the fungus Bipolaris leersiae revealed no significant dependence of this activity on absolute configuration.
• Enantiomeric excess of a cruciferous phytoalexin, spirobrassinin, and its enantiomeric enrichment in an achiral HPLC system

  K Monde, N Harada, M Takasugi, P Kutschy, M Suchy, M Dzurilla

  JOURNAL OF NATURAL PRODUCTS 63 9 1312 - 1314 2000年09月 [査読無し][通常論文]
   

  Enantiomeric purity of a cruciferous phytoalexin, spirobrassinin (1), was determined by chiral HPLC analysis,The enantiomeric excesses of two natural spirobrassinin fractions separated by nonchiral chromatography were considerably different. A significant enantiomeric enrichment was observed during the nonchiral chromatographic separation of an artificial enantiomeric mixture of 1.
• "Synthesis and Absolute Stereochemisty of a Cruciferous Phytoalexin, (–)-Spirobrassinin"

  K Monde, S Osawa, N Harada, M Takasugi, M Suchy, P Kutschy, M Dzurilla, E Balentova

  Chem. Lett. 29 8 886 - 887 2000年08月 [査読無し][通常論文]
   

  Synthetic (+/-)-spirobrassinin (1) was enantioresolved by a chiral auxiliary method giving (+)-1 and natural (-)-1. The absolute configuration was unambiguously determined by X-ray crystallography of a (1'S,4'R)-camphanoyl derivative of (+)-1. Consequently, natural (-)-1 has an S configuration. Their CD spectra supported this result.
• Design and preparation of polyphenyl distance markers for solid-state F-19 NMR

  K Monde, Y Tomita, ML Gilchrist, AE McDermott, K Nakanishi

  ISRAEL JOURNAL OF CHEMISTRY 40 3-4 301 - 306 2000年 [査読無し][通常論文]
   

  With C-13-labeled samples, it is possible to measure internuclear distances up to 7 Angstrom by solid-state NMR, thus providing a powerful tool for probing ligand-receptor interactions. However, limitations in measurable distances and appreciable natural abundant C-13 background signals present problems in solid-state C-13 NMR. In order to overcome these disadvantages, a set of reference compounds with known F-F distances, namely, quinolinol, p-biphenyl, and p-terphenyl-bearing trifluoromethyl and trifluoromethylthio groups, have been synthesized. The preparation of these reference compounds and means for diluting these references in solid-state NMR are described.
• Phytoalexins from Brassica (Cruciferae) as oviposition stimulants for the cabbage root fly, Delia radicum

  Robert Baur, Erich Staedler, Kenji Monde, Mitsuo Takasugi

  CHEMOECOLOGY 8 4 163 - 168 1998年12月 [査読無し][通常論文]
   

  Bacteria species known to induce the biosynthesis of crucifer-specific phytoalexins have earlier been shown to be associated with Delia flies. Eleven crucifer-specific phytoalexins and related synthetic compounds were applied on surrogate paper leaves and offered to cabbage root flies in oviposition assays. Since three of these compounds (methoxybrassinin, cyclobrassinin, brassitin) proved to be significantly stimulatory whereas the remaining metabolites had no effect, the reaction of the fly appears to be structure-specific. Inactive phytoalexins had no inhibitory effect on oviposition. 100 mu g of methoxybrassinin per surrogate leaf was as stimulatory as 0.05 gle (gram leaf equivalent) of a methanolic host-leaf (Brassica oleracea) extract. Thus the three active phytoalexins can explain only part of the activity of host-pant extracts but might induce a preference for infected plants.
• Organochlorine compounds from a terrestrial higher plant: Structures and origin of chlorinated orcinol derivatives from diseased bulbs of Lilium maximowiczii

  K Monde, H Satoh, M Nakamura, M Tamura, M Takasugi

  JOURNAL OF NATURAL PRODUCTS 61 7 913 - 921 1998年07月 [査読無し][通常論文]
   

  Seven chlorine-containing orcinol derivatives (2-8) and orcinol (9) have been isolated from diseased bulbs of the edible lily Lilium maximowiczii, and their structures have been elucidated. Six of the chlorinated orcinol derivatives (2, 4-8) showed antifungal activity. Because organochlorine compounds are rare in terrestrial higher plants, their biosynthetic origin was examined. These compounds were shown to be induced in intact bulb scales by UV irradiation or by inoculation with the pathogenic fungus Fusarium oxysporum f. sp. lilii. Biosynthetic studies suggested that these "natural organochlorine pesticides" are produced by enzymatic chlorination of orcinol (9) with chloroperoxidase and hydrogen peroxide, which are both induced in the plant tissue under stress conditions.
• Synthesis and optical resolution of a fluorescent chiral calix[4]arene with two pyrene moieties forming an intramolecular excimer

  T Jin, K Monde

  CHEMICAL COMMUNICATIONS 1998 13 1357 - 1358 1998年07月 [査読無し][通常論文]
   

  An inherently fluorescent chiral calix[4]arene 2 with two pyrene moieties forming an intramolecular pyrene excimer has been synthesized and optically resolved by an HPLC method using a chiral-packed column.
• Trapping experiment with aniline for a biosynthetic intermediate of sulfur-containing cruciferous phytoalexins

  K Monde, A Tanaka, M Takasugi

  JOURNAL OF ORGANIC CHEMISTRY 61 25 9053 - 9054 1996年12月 [査読無し][通常論文]
  
• Identification of an ornithine-containing lipid from Cytophaga johnsonae Stanier strain C21 by H-1-NMR

  H Okuyama, K Monde

  CHEMISTRY AND PHYSICS OF LIPIDS 83 2 169 - 173 1996年09月 [査読無し][通常論文]
   

  The structure of an ornithine-containing lipid from Cytophaga johnsonae Stanier strain C21 was determined by H-1-NMR analysis of its major molecular species (compound 1) consisting of iso-3-hydroxy heptadecanoic (iso-3-OH-17:0) and iso-pentadecanoic acids (iso-15:0). The NOESY spectrum showed the cross peaks between alpha-NH of ornithine and two protons of the alpha-methylene moiety of iso-3-OH-17:0. The delta-amino group of the ornithine did not form an amide linkage with any fatty acid. Thus, the structure of the ornithine-containing lipid was iso-3-hydroxy heptadecanoic acid, alpha-amide linked to ornithine and esterified to iso-15:0.
• 栽培ヒラタケに腐敗病を起こす日本産 Pseudomonas tolaasii の産生する毒素とその生物活性

  白田 昭, 菅谷 和寿, 高杉 光雄, 門出 健次

  日本植物病理学会報 61 5 493 - 502 1995年10月
• STUDIES ON STRESS METABOLITES .20. 3 SULFUR-CONTAINING STRESS METABOLITES FROM JAPANESE RADISH

  K MONDE, M TAKASUGI, A SHIRATA

  PHYTOCHEMISTRY 39 3 581 - 586 1995年06月 [査読無し][通常論文]
   

  Three new brassinin related stress metabolites, named brassitin, N-methoxyspirobrassinol methyl ether and N-methoxyspirobrassinol, were isolated from the Japanese radish 'Daikon' (Raphanus sativus var. hortensis) after inoculation with Pseudomonas cichorii. Their structures have been established on the basis of spectroscopic data and chemical reactions. N-Methoxyspitobrassinol has an unusual hemi-aminal structure, and occurs as a mixture of diastereomers. The occurrence of N-methoxyspirobrassinol methyl ether and N-methoxyspirobrassinol suggests the involvement of oxidized intermediates in the biosynthesis from brassinin to spirobrassinin.
• No involvement of methoxybrassinin in the biosynthesis of cyclobrassinin

  Kenji Monde, Kimio Tamura, Mitsuo Takasugi

  Phytochemistry 39 3 587 - 589 1995年 [査読無し][通常論文]
   

  Feeding experiments with Pseudomonas cichorii-inoculated Japanese radish roots indicated that methoxybrassinin is not derived from brassinin, and that cyclobrassinin is not biosynthesized from methoxybrassinin. © 1995.
• A NEW APPROACH IN EXCITON-COUPLED CIRCULAR-DICHROISM (ECCD) - INSERTION OF AN AUXILIARY STEREOGENIC CENTER

  RV PERSON, K MONDE, HU HUMPF, N BEROVA, K NAKANISHI

  CHIRALITY 7 3 128 - 135 1995年 [査読無し][通常論文]
   

  There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH=C=CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. (C) 1995 Wiley-Liss, Inc.
• Cruciferous Phytoalexins

  Kenji Monde, Mitsuo Takasugi

  Journal of Pesticide Science 20 3 339 - 343 1995年 [査読有り][通常論文]
  
• STUDIES ON STRESS METABOLITES .19. BIOSYNTHESIS OF CRUCIFEROUS PHYTOALEXINS

  K MONDE, M TAKASUGI, T OHNISHI

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 116 15 6650 - 6657 1994年07月 [査読無し][通常論文]
   

  We report the results of biosynthetic studies on the sulfur-containing indole phytoalexins, antimicrobial compounds produced by plants after exposure to microorganisms. Feeding experiments with UV-irradiated sliced turnip root (Brassica campestris ssp. rapa) revealed that spirobrassinin (3) is formed via brassinin (1a) and that 1a is biosynthesized by the intramolecular rearrangement of L-tryptophan to form unstable indol-3-ylmethylisothiocyanate (10a). Trapping experiments of 10a with NaSCH3 and formation of PhCH(2)NH-CS-SCH3 (14) on administration of benzyl isothiocyanate supported the presence of the labile isothiocyanate intermediate. Feeding experiments of a mixture of L-[methyl-H-3(3)]methionine and L-[S-35]methionine revealed that the methylthio group of methionine is incorporated into 1a as an unusual intact unit. Incorporation of L-[S-35]cysteine into la and 3 indicated the origin of another sulfur atom. These studies suggest that the biosynthetic pathway of cruciferous phytoalexins is at least partially linked to one of the indole glucosinolates which are typical components of crucifers. Structures of metabolites of 2-methylbrassinin (16) imply the presence of an oxidized intermediate between 1a and other cruciferous phytoalexins.
• Dehydro-4-methoxycyclobrassinin, a Sulfur-containing Phytoalexin Isolated from Turnip Brassica campestris L. ssp. rapa

  Mitsuo Takasugi, Kenji Monde, Kimio Tamura, Kensuke Kobayashi, Masanori Somei

  HETEROCYCLES 38 2 263 - 263 1994年
• STUDIES ON STRESS METABOLITES .17. YURINELIDE, A NOVEL 3-BENZYLIDENE-1,4-BENZODIOXIN-2(3H)-ONE PHYTOALEXIN FROM LILIUM-MAXIMOWICZII

  K MONDE, M KISHIMOTO, M TAKASUGI

  TETRAHEDRON LETTERS 33 37 5395 - 5398 1992年09月 [査読無し][通常論文]
   

  Infected lily bulbs afforded the first natural 3-benzylidene-1,4-benzodioxin-2(3H)-one derivative, yurinelide 1. The structure was elucidated by interpretation of the spectral data and chemical reactions.
• Lipoamino acids and sulfonoplipids in Cytophaga johnsonae Stanier strain C21 and six related species of Cytophaga

  Ryoh Kawazoe, Kenji Monde, Wolfgang Reichardt, Hidetoshi Okuyama

  Archives of Microbiology 158 3 171 - 175 1992年08月 [査読有り][通常論文]
   

  Cytophaga johnsonae Stanier strain C21 (C. johnsonae C21) contains phosphatidylethanolamine (PE), an unusual glycine-containing lipid (glycine lipid), and two kinds of unidentified lipid as major lipid components. One of the latter lipids was identified by chemical and physicochemical methods as iso-3-hydroxy fatty acid, α-amide linked to ornithine and esterified to iso-nonhydroxy fatty acid (ornithine lipid). The other lipid was identified as a sulfonolipid by a tracer experiment using 35S. PE, glycine lipid and sulfonolipid were found in all seven species of Cytophage examined, namely, C. huchinsonii, C. heparina, C. johnsonae C21, C. aquatilis, and three unidentified species of Cytophaga. However, ornithine lipid was found only in the latter five species. By contrast, a serine-containing lipid, which is a specific lipid component of Flavobacterium species, was not found in any species of Cytophaga examined. The possible use and significance of amino acid-containing lipids and sulfonolipids as chemosystematic markers of the Cytophaga species are discussed. © 1992 Springer-Verlag.
• STUDIES ON STRESS METABOLITES .16. HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF CRUCIFEROUS PHYTOALEXINS USING COMPLEX TERNARY MOBILE PHASE GRADIENTS

  K MONDE, M TAKASUGI

  JOURNAL OF CHROMATOGRAPHY 598 1 147 - 152 1992年05月 [査読無し][通常論文]
   

  A reversed-phase high-performance liquid chromatographic analysis of cruciferous phytoalexins, antimicrobial compounds synthesized de novo by plants after exposure to microorganisms, was performed using an acetonitrile-methanol-water complex solvent gradient system. A well resolved chromatogram of thirteen phytoalexins and three related indole metabolites isolated from cruciferous plants was obtained by this method. Accumulation of phytoalexins in Pseudomonas cichorii-inoculated turnip tissue was followed by this high-performance liquid chromatographic analysis.
• STUDIES ON STRESS METABOLITES .14. BIOSYNTHESIS OF CRUCIFEROUS PHYTOALEXINS - THE INVOLVEMENT OF A MOLECULAR REARRANGEMENT IN THE BIOSYNTHESIS OF BRASSININ

  K MONDE, M TAKASUGI

  JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS 1991 22 1582 - 1583 1991年11月 [査読無し][通常論文]
   

  Incorporation of [4'-H-2], [2-C-13]tryptophan, and [methyl-(H3)-H-2]brassinin 1 into spirobrassinin 3 by UV-irradiated turnip tissue indicates that spirobrassinin 3 is formed via brassinin 1, which is biosynthesized from tryptophan by a pathway involving a molecular rearrangement and possible formation of indol-3-ylmethyl isothiocyanate 6a.
• TIME-COURSE STUDIES OF PHYTOALEXINS AND GLUCOSINOLATES IN UV-IRRADIATED TURNIP TISSUE

  K MONDE, M TAKASUGI, JA LEWIS, GR FENWICK

  ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES 46 3-4 189 - 193 1991年03月 [査読無し][通常論文]
   

  Sliced turnip root (Brassica campestris L. ssp rapa) was irradiated for a total of 20 min with a 15 W germicidal lamp and the tissue incubated at 25-degrees-C. The effects of such treatment on indole phytoalexins (methoxybrassinin (I); brassinin (II); cyclobrassinin (III); spirobrassinin (IV) and glucosinolates were determined using high performance liquid chromatography procedures. Accumulation of phytoalexins I-III was evident within 8 h of irradiation, whilst formation of spirobrassinin was evident only after 24 h. Maximal levels of III and IV (> 100-mu-g g-1 freeze dried tissue) were greater than those of I and II (27 and 17-mu-g g-1, respectively). The individual glucosinolate levels were affected in a complex manner; whilst most glucoinolates decreased on storage, the levels of indole glucosinolates, glucobrassicin (XI) and 1-methoxyglucobrassicin (XIII), increased until 5 to 6 days after irradiation and thereafter declined. Whilst structural features of I-IV, XI and XIII suggest close biosynthetic relationships between these classes of biologically-active indoles, further studies are needed to establish this point unambiguously.
• BRASSICANAL C AND 2-DIOXINDOLES FROM CABBAGE

  K MONDE, K SASAKI, A SHIRATA, M TAKASUGI

  PHYTOCHEMISTRY 30 9 2915 - 2917 1991年 [査読無し][通常論文]
   

  Brassicanal C, a new sulphur-containing phytoalexin, and two dioxindoles were isolated from cabbage inoculated with Pseudomonas cichorii. Brassicanal C was shown to possess a unique sulphinate structure on the basis of spectroscopic data and optical activity. One of the dioxindoles, dioxibrassinin, appears structurally to be a possible precursor to spirobrassinin.
• STUDIES ON STRESS METABOLITES .15. METHOXYBRASSENIN-A AND METHOXYBRASSENIN-B, SULFUR-CONTAINING STRESS METABOLITES FROM BRASSICA-OLERACEA VAR CAPITATA

  K MONDE, K SASAKI, A SHIRATA, M TAKASUGI

  PHYTOCHEMISTRY 30 12 3921 - 3922 1991年 [査読無し][通常論文]
   

  Two methoxybrassinin-related stress metabolites, named methoxybrassenins A and B, were isolated from Brassica oleracea var. capitata inoculated with Pseudomonas cichorii. Their structures have been elucidated by spectroscopic and chemical methods. The unusual NMR spectrum of methoxybrassenin B is also discussed in connection with its structure.
• STUDIES ON STRESS METABOLITES .11. TOTAL SYNTHESIS OF LETTUCENIN-A, A GUAIANOLIDE PHYTOALEXIN FROM LACTUCA-SATIVA VAR CAPITATA

  K MONDE, M TAKASUGI, N KATSUI, T MASAMUNE

  CHEMISTRY LETTERS 19 8 1283 - 1286 1990年08月 [査読無し][通常論文]
  
• STUDIES ON STRESS METABOLITES .8. BRASSICANAL-A AND BRASSICANAL-B, NOVEL SULFUR-CONTAINING PHYTOALEXINS FROM THE CHINESE CABBAGE BRASSICA-CAMPESTRIS L SSP PEKINENSIS

  K MONDE, N KATSUI, A SHIRATA, M TAKASUGI

  CHEMISTRY LETTERS 19 2 209 - 210 1990年02月 [査読無し][通常論文]
  
• A guaianolide phytoalexin, cichoralexin, from Cichorium intybus

  Kenji Monde, Toyohisa Oya, Akira Shirata, Mitsuo Takasugi

  Phytochemistry 29 11 3449 - 3451 1990年 [査読無し][通常論文]
   

  A sesquiterpenoid phytoalexin, cichoralexin was isolated from Cichorium intybus inoculated with Pseudomonas cichorii. Its structure has been elucidated by spectroscopic methods. © 1990.
• STUDIES ON STRESS METABOLITES .9. 4-METHOXYBRASSININ, A SULFUR-CONTAINING PHYTOALEXIN FROM BRASSICA-OLERACEA

  K MONDE, K SASAKI, A SHIRATA, M TAKASUGI

  PHYTOCHEMISTRY 29 5 1499 - 1500 1990年 [査読無し][通常論文]
  
• STUDIES ON STRESS METABOLITES .7. NOVEL SULFUR-CONTAINING PHYTOALEXINS FROM THE CHINESE CABBAGE BRASSICA-CAMPESTRIS L SSP PEKINENSIS (CRUCIFERAE)

  M TAKASUGI, K MONDE, N KATSUI, A SHIRATA

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 61 1 285 - 289 1988年01月 [査読無し][通常論文]
  
• ANTIFUNGAL COMPOUNDS FROM DIOSCOREA-BATATAS INOCULATED WITH PSEUDOMONAS-CICHORII

  M TAKASUGI, S KAWASHIMA, K MONDE, N KATSUI, T MASAMUNE, A SHIRATA

  PHYTOCHEMISTRY 26 2 371 - 375 1987年 [査読無し][通常論文]
  
• STUDIES ON STRESS METABOLITES .6. SPIROBRASSININ, A NOVEL SULFUR-CONTAINING PHYTOALEXIN FROM THE DAIKON RHAPHANUS-SATIVUS L VAR HORTENSIS (CRUCIFERAE)

  M TAKASUGI, K MONDE, N KATSUI, A SHIRATA

  CHEMISTRY LETTERS 16 8 1631 - 1632 1987年 [査読無し][通常論文]
  

書籍

• 機器分析ハンドブック２ 高分子・分離分析編

  床波 志保, 前田 耕治, 安川 智之 (担当:分担執筆範囲:10章 旋光度と円偏光二色法（CD）)
  化学同人 2020年10月 (ISBN: 9784759820225) vii, 177p 140-153
• 化学便覧 基礎編 改訂6版

  日本化学会 (担当:分担執筆範囲:15章 分光学的性質 ―生体物質の円二色性―)
  丸善出版㈱ 2020年 (ISBN: 9784621097243) 97-98
• セラミド研究の新展開 ～基礎から応用へ～

  セラミド研究会 (担当:分担執筆範囲:第33章 ”天然物を利用したセラミド関連物質の化学合成戦略”)
  食品化学新聞社 2019年 (ISBN: 9784916143358) 337 278-285
• キラル化学 : その起源から最新のキラル材料研究まで（CSJ Current Review, 13）

  日本化学会 (担当:分担執筆範囲:Chap 2 ”赤外円二色スペクトルによる絶対配置決定”)
  化学同人 2013年 (ISBN: 9784759813739) 43-49
• 「赤外円二色性スペクトル法における新展開」

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  高分子 2012年 779-780
• Comprehensive Chiroptical Spectroscopy

  Berova Nina 
  John Wiley & Sons 2011年 (ISBN: 9780470641354)
• 高分子分析技術最前線

  高分子学会 
  共立出版 2007年 (ISBN: 9784320043794)
• 「第五版実験化学講座,１４巻, 有機化合物の合成（Ⅱ）」

  丸善株式会社 2005年
• 糖鎖生物学入門

  Taylor Maureen, Drickamer Kurt 著, 西村 紳一郎, 門出 健次 
  化学同人 2005年 (ISBN: 9784759810356)
• 「植物病害の化学」

  学会出版センター 1997年
• 「２４章第３節第４項 絶対立体配置」, 有機合成実験法ハンドブック 第２版

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  丸善出版

その他活動・業績

• 研究者にもっと研究時間を

  門出 健次 有機合成化学協会誌 82 (2) 115 -115 2024年02月
• ケモエンザイマティカルな長鎖塩基の調製と樹脂固定型グルタルアルデヒドによる効率的精製法

  門出 健次, 村井 勇太 生化学 92 (2) 272 -277 2020年04月 [査読無し][通常論文]
  
• Vibrational CD spectroscopy as a powerful tool for chiral analysis of flavor compounds

  Kenji Monde, Atsufumi Nakahashi, Nobuaki Miura, Tohru Taniguchi, Yoshihiro Yaguchi, Daisuke Sugimoto, Makoto Emura ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 248 2014年08月 [査読無し][通常論文]
  
• 赤外円二色性スペクトル法における新展開

  門出 健次 高分子 61 (10) 779 -780 2012年10月01日
• キラル多核金属錯体の振動円二色性スペクトルによる研究

  佐藤久子, 谷口透, 門出健次, 福田豊, 山岸晧彦 錯体化学討論会講演要旨集 57th 192 2007年09月10日 [査読無し][通常論文]
  
• A challenge to describe the functional networks of glycoconjugates: "Glyconet" in a database "Glycoconjugate Data Bank"

  Nobuaki Miura, Kazuko Hirose, Tomonori Ito, Ryo Hashimoto, Nobuhiro Fukushima, Kenji Monde, Shin-Ichiro Nishimura GLYCOBIOLOGY 16 (11) 1123 -1124 2006年11月 [査読無し][通常論文]
  
• A glycomic approach to drug resistance: Direct interaction between Cisplatin and N-glycans

  Hiroaki Nakagawa, Shinji Hayashi, Shigeaki Abe, Noriko Nagahori, Kenji Monde, Miki Ichikawa-Ohira, Hirosato Kondo, Shin-Ichi Akiyama, Kisaburo Deguchi, Akira Nakagawara, Shin-Ichiro Nishimura GLYCOBIOLOGY 16 (11) 1150 -1150 2006年11月 [査読無し][通常論文]
  
• Novel chiroptical analysis of glycoconjugates by Vibrational Circular Dichroism (VCD)

  Kenji Monde, Tohru Taniguchi, Masami Fukuzawa, Mai Hashimoto, Atsufumi Nakahashi, Nobuaki Miura, Shin-Ichiro Nishimura GLYCOBIOLOGY 16 (11) 1136 -1137 2006年11月 [査読無し][通常論文]
  
• トリスキレート型金属錯体の光学分割とVCD

  佐藤久子, 谷口透, 門出健次, 西村紳一郎, 山岸皓彦 錯体化学討論会講演要旨集 56th 326 2006年09月08日 [査読無し][通常論文]
  
• トリスおよびビスアセチルアセトナト金属錯体のVCD測定と理論計算

  佐藤久子, 谷口透, 門出健次, 西村紳一郎, 山岸晧彦 錯体化学討論会講演要旨集 56th 34 2006年09月08日 [査読無し][通常論文]
  
• キトサン骨格を有する機能性糖鎖クラスターの開発

  李 学兵, 渡辺 慎也, 鈴木 隆, 鈴木 康夫, 渡邊 美帆, 名取 泰博, 西川 喜代孝, 喜多 英二, 門出 健次, 西村 紳一郎 キチン・キトサン研究 = Chitin and chitosan research 11 (2) 120 -121 2005年07月01日 [査読無し][通常論文]
  
• Specific band observed in VCD predicts the anorneric configuration of carbohydrates (vol 126, pg 9496, 2004)

  K Monde, T Taniguchi, N Miura, SI Nishimura JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 127 (16) 6133 -6133 2005年04月 [査読無し][通常論文]
  
• Structural assignment of isomeric 2-aminopyridine-derivatized oligosaccharides using MSn spectral matching (vol 18, pg 385, 2004)

  Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura RAPID COMMUNICATIONS IN MASS SPECTROMETRY 19 (4) 588 -588 2005年 [査読無し][通常論文]
  
• Vibrational circular dichroism: Chiroptical analysis of biomolecules

  T Taniguchi, N Miura, SI Nishimura, K Monde MOLECULAR NUTRITION & FOOD RESEARCH 48 (4) 246 -254 2004年09月 [査読無し][通常論文]
  
• Synthesis of 4-fluorinated UDP-MurNAc pentapeptide as an inhibitor of bacterial growth (vol 6, pg 1753, 2004)

  T Ueda, F Feng, R Sadamoto, K Niikura, K Monde, SI Nishimura ORGANIC LETTERS 6 (14) 2489 -2489 2004年07月 [査読無し][通常論文]
  
• キトサンを主鎖骨格とした機能性糖鎖クラスター

  李 学兵, 渡辺 慎也, 鈴木 隆, 鈴木 康夫, 名取 泰博, 西川 喜代孝, 門出 健次, 西村 紳一郎 キチン・キトサン研究 = Chitin and chitosan research 10 (2) 204 -205 2004年07月01日 [査読無し][通常論文]
  
• 糖鎖付加インスリンのデザインと機能

  佐藤公昭, 貞許礼子, 藤谷直樹, 中原拓, FENG F, 新倉謙一, 門出健次, 西村紳一郎, 近藤裕郷 高分子学会予稿集(CD-ROM) 53 (1) IH14 2004年05月10日 [査読無し][通常論文]
  
• 71(P-61) 振動円二色性(VCD)スペクトルによる複合糖質等の立体化学研究(ポスター発表の部)

  谷口 透, 三浦 信明, 内田 直人, 西村 紳一郎, 門出 健次 天然有機化合物討論会講演要旨集 46 (0) 401 -406 2004年 [査読無し][通常論文]
   

  Chiral molecules exhibit circular dichroism (CD), the differential absorption of left versus right circularly polarized light, and the spectroscopies have been useful method for determining the absolute configuration. Recently, the measurement of CD in an infrared region, i.e. vibrational circular dichroism (VCD), has been advanced instrumentally and theoretically. VCD has some advantages over conventional electronic circular dichroism (ECD) by the applicability to all organic molecules and the reliability of ab initio quantum calculations. We apply this powerful technique to the determination of the absolute stereochemistry of some cruciferous phytoalexin-related compounds and to analysis of glycoconjugates. The determination of the absolute configuration of cruciferous phytoalexin-related compounds A number of cruciferous phytoalexin studies have been reported so far, but most of their absolute stereochemistry is still to be investigated. So we applied the VCD spectroscopy to determine the absolute configuration of dioxibrassinin (1) and 3-cyanomethyl-3-hydroxyoxindole (2). Compounds 1 and 2 were synthesized and their VCD spectra were measured. The comparison of observed VCD spectra and calculated ones indicated that their stereochemistry are both S. This is the first case of the determination of absolute stereochemistry of chiral tertiary alcohols by VCD. Application of VCD to carbohydrates Recently, the biological significance of carbohydrates have been recognized and analytical studies of carbohydrates have been widely investigated. Most analyses have been based on achiral methods such as NMR or MS in spite of their chiral properties. We considered that the detailed stereochemical information could be extracted using VCD. Various carbohydrates have been measured to construct an extensive database aiming to create a methodology for VCD pattern discrimination of the carbohydrates. The database in the fingerprint region indicated that sugars with the axial glycosidic linkage showed a negative, sharp and intense VCD band, named "Glycoside band" at around 1145 cm^<-1>. The applicability of the Glycoside band was demonstrated by quantifying α-β ratio of mixture samples and monitoring of an enzymatic reaction. In the C-H stretching region, we found the stereochemistry of single chiral center in the presence of multiple such centers could be extracted through the vibrational chirality transfer phenomenon. Also, VCD in this region was indicated to be a sensitive probe of glycosidic linkage sites. In conclusion, by using the VCD database and the proposed spectra-structure correlations, VCD will be an effective tool in carbohydrate analysis.
• 糖鎖のDFT法によるコンフォメーション解析と振動円二色性(VCD)スペクトルによる検証

  三浦 信明, 谷口 透, 門出 健次, 西村 紳一郎 基礎有機化学討論会要旨集（基礎有機化学連合討論会予稿集） 17 (0) 51 -51 2004年 [査読無し][通常論文]
   

  糖鎖は不斉炭素の集合体であり、その配座解析の確固たる方法論が未だにない。我々は配座解析の強力なツールとして分子軌道法を用い、不斉性を検出可能な振動領域円二色性スペクトルを計算することによって、測定されたスペクトルを再現することによって糖鎖の配座を混合比のレベルでの解析を行う。
• N-glycan patterns of human serum in rheumatoid arthritis

  M Hato, H Nakagawa, Y Takegawa, K Deguchi, K Monde, N Iwasaki, A Minami, H Kondo, SI Nishimura GLYCOBIOLOGY 13 (11) 870 -870 2003年11月 [査読無し][通常論文]
  
• Structural assignment of isomeric 2-aminopyridine derivatized oligosaccharides using Ms-n spectral matching

  Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura GLYCOBIOLOGY 13 (11) 844 -845 2003年11月 [査読無し][通常論文]
  
• Structures of N-glycan from human dermis

  R Uematsu, H Nakagawa, K Deguchi, M Ota, K Yokota, H Shimizu, K Monde, SI Nishimura GLYCOBIOLOGY 13 (11) 846 -846 2003年11月 [査読無し][通常論文]
  
• Glycoblotting: Synthetic nanoparticles for rapid isolation and analysis of glycopatterns

  SI Nishimura, K Niikura, N Nagahori, R Uematsu, H Nakagawa, S Abe, H Moriyama, R Sadamoto, K Deguchi, K Monde, H Kondo GLYCOBIOLOGY 13 (11) 843 -844 2003年11月 [査読無し][通常論文]
  
• 不凍糖タンパク質モデル分子の設計と機能発現メカニズムの解明

  立花裕樹, 五十嵐幸太, 藤谷直樹, 津田栄, 門出健次, 西村紳一郎 高分子学会予稿集 52 (13) 3755 -3756 2003年09月10日 [査読無し][通常論文]
  
• 抗インフルエンザウイルス活性を有する環状糖ペプチドの設計と評価

  太田尚志, 藤谷直樹, 三浦信明, 新倉謙一, 鈴木隆, 鈴木康夫, 門出健次, 西村紳一郎 高分子学会予稿集 52 (13) 3789 -3790 2003年09月10日 [査読無し][通常論文]
  
• Synthesis and characterization of functional glycolipid LB membrane.

  N Nagahori, R Sadamoto, K Niikura, K Monde, SI Nishimura ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 226 U200 -U200 2003年09月 [査読無し][通常論文]
  
• Stereochemical chiral analysis of carbohydrates by vibrational circular dichroism.

  K Monde, T Taniguchi, N Miura, SI Nishimura ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 226 U213 -U213 2003年09月 [査読無し][通常論文]
  
• 抗インフルエンザウイルス活性を有する環状糖ペプチドの設計と評価

  太田尚志, 藤谷直樹, 三浦信明, 新倉謙一, 鈴木隆, 鈴木康夫, 門出健次, 西村紳一郎 日本化学会北海道支部研究発表会講演要旨集 2003 56 2003年07月01日 [査読無し][通常論文]
  
• 21 氷晶成長阻害活性を有する糖ペプチドポリマーの合成と構造活性相関(口頭発表の部)

  立花 裕樹, 五十嵐 幸太, 門出 健次, 西村 紳一郎, 津田 栄 天然有機化合物討論会講演要旨集 44 (0) 121 -126 2002年 [査読無し][通常論文]
   

  Antifreeze glycoproteins [AFGPs: {Ala-Thr(Galβ1-3GalNAcα)-Ala}_n, n=4-50] in the serum of polar fishes have been known to depress the freezing point of their blood and help them to survive at the temperature below-1.9℃[1]. Though it is widely accepted that AFGPs bind to the ice surface and prevent its growth, the definitive molecular mechanism of the action has not been solved yet. In this study, structure-activity relationships in AFGPs were studied toward understanding of the mechanism, thorough chemical syntheses, activity evaluations, and conformational analyses of the AFGP and its analogues, in which sugar or peptide moieties were different from those of the wild-type AFGP. The AFGP (1) and its analogues (2-8) were successfully synthesized via simple polymerization of their repeating unit using a DPPA method without any protection of sugar -OH groups [2]. Additionally, sialyl T-bearing glycopolypeptide (9) was successfully prepared through enzymatic elongation of a sialic acid residue to C-3 position of the galactose residue in the AFGP (1), indicating the broad applicability of this methodology for the syntheses of various glycopeptide polymers. In the evaluation assay of the antifreeze activity, artificial AFGP (1) showed similar activity as that of the wild-type AFGP. On the contrary, neither an AFGP repeating unit glycopeptide (19) nor a sugar-lacked polypeptide (poly-ATA, 8) shows the activity. Interestingly, AFGP analogs having GalNAc (2) or LacNAc (3) as sugar moiety showed similar activities as AFGP, while that of Galactose (4), Lactose (5), β-O-linked (6), and ASA (7) did not. These results clearly indicate the importance of i) repeating structure of glycopeptide, ii) NHAc group at C-2 position of the sugar moiety directly attached to the peptide, iii) α-glycosidic linkage between the sugar and the threonyl residue, for the specific interaction with ice. Furthermore, secondary structural analyses of the synthetic compounds were carried out by means of a CD spectroscopic method, in order to clarify the relationships between their conformations and their activities. The CD spectra of active compounds (1-3) were obviously different from those of inactive analogues (4-8), suggesting the presence of an ordered structure, but not α-helix.
• CRUCIFEROUS PHYTOALEXINS

  K MONDE, M TAKASUGI JOURNAL OF PESTICIDE SCIENCE 20 (3) 339 -343 1995年 [査読無し][通常論文]
  
• STUDIES ON STRESS METABOLITES .18. DEHYDRO-4-METHOXYCYCLOBRASSININ, A SULFUR-CONTAINING PHYTOALEXIN ISOLATED FROM TURNIP BRASSICA-CAMPESTRIS L SSP RAPA

  K MONDE, K TAMURA, M TAKASUGI, K KOBAYASHI, M SOMEI HETEROCYCLES 38 (2) 263 -267 1994年02月 [査読無し][通常論文]
   

  Isolation, structure elucidation, and synthesis of dehydro-4-methoxycyclobrassinin (1), a turnip phytoalexin possessing a novel heterocyclic system, are described.
• 植物の生体防御機構 - アブラナ科植物のファイトアレキシン -

  門出 健次 化学と工業 = Chemistry and chemical industry 45 (2) 295 -299 1992年02月01日

特許

• 特願2021-102280:抗ウイルス剤  2021年06月21日

  門出 健次, 村井 勇太, 五十嵐 靖之, 臼杵 靖剛, 澤 洋文, 大場 靖子, 佐々木 道仁  国立大学法人北海道大学
• 特願2021-041717:化合物、その製造方法、複合体および短波赤外蛍光剤  2021年03月15日

  神 隆, マカナハリ マデゴウダ マハデバ スワミィ, 門出 健次, 村井 勇太  国立研究開発法人理化学研究所, 国立大学法人北海道大学
• 特願2020-117350:トリグリセリドの代謝能に関する値の取得方法、疾患の情報の提示方法、疾患の鑑別情報の提示方法、治療の有効性情報の提示方法、検査試薬、及び検査キット  2020年07月07日

  平野 賢一, 原 康洋, 柏木 浩和, 鈴木 朗, 神 隆, 門出 健次, 村井 勇太  国立大学法人大阪大学, 国立研究開発法人理化学研究所, 国立大学法人北海道大学
• 特開2019-104692:スフィンゴミエリン合成酵素阻害剤  2019年06月27日

  門出 健次, 村井 勇太, マカナハリ マデゴウダ マハデバ スワミィ  国立大学法人北海道大学
• 特開2019-104691:スフィンゴミエリン合成酵素阻害剤  2019年06月27日

  門出 健次, 村井 勇太, マカナハリ マデゴウダ マハデバ スワミィ  国立大学法人北海道大学
• 特開2017-128518:SMS2阻害活性を有するセラミド誘導体  2017年07月27日

  門出 健次, ハンマン モスタファ アハメド サベット アハメド, 須賀 好子, 吉田 裕, 松村 謙一  塩野義製薬株式会社, 国立大学法人北海道大学  201703000395148174
• 特開2016-079161:糖スフィンゴシン及びスフィンゴ塩基の製造方法  2016年05月16日

  門出 健次, 五十嵐 靖之, 臼杵 靖剛, ボメゴウダ シッダバサーブ ゴウダ  国立大学法人北海道大学  201603017183529154
• 特開2008-228688:生物挙動コントロール方法及びその装置  2008年10月02日

  門出 健次, 山口 淳二, 深澤 知行  国立大学法人 北海道大学, 日本分光株式会社  201403039448597376
• 特開2008-189705:撥水性および撥油性表面を有する物品およびその製造法  2008年08月21日

  辻井 薫, 黒木一誠, 門出健次  国立大学法人 北海道大学
• 特開2005-306836:α-アミラーゼ阻害剤  2005年11月04日

  門出 健次, 西村 紳一郎, 内田 直人, 三浦 信明, 森山 英樹, 前川 宣彦  株式会社生物有機化学研究所
• 特開2005-69998:VCDを利用した糖の分析法  2005年03月17日

  門出 健次, 谷口 透, 三浦 信明, 西村 紳一郎  塩野義製薬株式会社
• 特願2003-27690:糖ペプチドおよびそのプロテオグリカンイニシエーターとしての使用  2003年02月04日

  西村 紳一郎, 佐藤 史洋, 門出 健次  西村 紳一郎

受賞

• 2018年 モレキュラー・キラリティー・アワード
   

  受賞者: 門出 健次
• 1992年 第7回若い世代の特別講演賞
  
• 1992年 September, 1992 7th Special Lecture Award for the younger generation (The Chemical Society of Japan)
  

共同研究・競争的資金等の研究課題

• スフィンゴミエリン合成酵素２阻害剤による腫瘍免疫亢進を介した新規抗癌治療の開発

  日本学術振興会：科学研究費助成事業

  研究期間 : 2022年04月 -2025年03月 

  代表者 : 岡崎 俊朗, 村井 勇太, 谷口 真, 門出 健次
• VCD励起子キラリティー法による立体構造解析法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2019年04月 -2023年03月 

  代表者 : 門出 健次, 谷口 透, 村井 勇太

   

  赤外円二色性スペクトル（VCD）は、キラルな分子の立体構造を解析する分光法である。我々は「VCD励起子キラリティー」と命名した理論計算を必要としない最初の非経験的法則を見出している。本法はカルボニル基の二つの発色団の相互作用を基盤としており、極めて高感度である。本研究では、VCD励起子キラリティー法を１）アルキン、アジド、ニトリルなどの他のIR官能基に関しても適用可能であるか検証すること。２）本法を生体関連中分子等の立体構造解析へ適用すること。３）赤外円二色性スペクトル（VCD）と同様な振動分光であるキラルラマンスペクトル（ROA）での本法の展開性を検証することを目的としている。
• フルーツ由来マラバリコーンの肥満抑制コミュニケーションの解明と医薬展開

  日本学術振興会：科学研究費助成事業 新学術領域研究(研究領域提案型)

  研究期間 : 2020年04月 -2022年03月 

  代表者 : 門出 健次

   

  現在、我が国の死亡原因はガンに続き、心疾患、脳血管疾患が上位を占める。その要因は主として脂質代謝疾患による脂質蓄積の異常が原因であると考えられている。脂質合成酵素の内、スフィンゴミエリン合成酵素(SMS)は、その阻害により、ガン免疫亢進、アミロイドβのクリアランス等に効果があることが知られている。我々は、フルーツより得られたマラバリコーンが高いSMS阻害能及び肥満抑制効果を有することを見出している。しかし、マラバリコーンによる肥満抑制効果についての詳細な分子機構は明らかとなっていない。本研究では、この分子機構を明らかにすることにより、ガン、肥満抑制に関する機構の情報を得ること目的としている。
• 化合物先行型脂質疾患バイオマーカーの探索研究

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  研究期間 : 2017年06月 -2020年03月 

  代表者 : 門出 健次, 村井 勇太

   

  スフィンゴ脂質の基本構造であるスフィンゴシン骨格は、セリンとパルミトイルCoAから生合成される。ごく最近、生活習慣病等の患者から異常スフィンゴ脂質が発見された。これは、セリンの代わりにアラニンとパルミトイルCoAから生合成されたものであり、強い細胞毒性を有すると共に、生活習慣病の鋭敏なバイオマーカーになる可能性が期待されている。スフィンゴシン類の生合成系には、セリン、アラニン、グリシン以外のアミノ酸も取り込まれる可能性があると考え、標品としての対応する変異スフィンゴシンを化学合成した。昨年度は、L-フェニルアラニン、L-アラニン、L-トリプトファン、L-ロイシンからのスフィンゴシン様化合物に成功した。本年度は、L-システイン、L-スレオニンを実施した。システインについてはチオール基の独自の反応性のため、保護基の導入を念頭においた。そのため、2位のアミノ基を利用した5員環形成による分子内保護法を当初実施した。従来法の応用によりHorner-Wadsworth-Emmons 反応により増炭反応には成功したが、還元反応が良好に進行せず、別ルートによる合成を試みた。チオール基の特殊な反応性による合成問題を解決するために、比較的後半にチオール基を導入することとした。スフィンゴシンの合成を基本として進め、1位の水酸基に脱離基を導入した後、チオ酢酸で置換反応を行った。その後、加水分解、脱保護により目的の化合物を得ることに成功した。また。L-スレオニンを原料として、従来法によりスレオニン部分を頭部に有する変異スフィンゴシンの合成に成功した。将来的なセラミド類ライブラリー化を念頭に、アミノ基のアシル化を実施した。通常のセリン、アラニン、システイン、ロイシン、フェニルアラニンタイプについて、それぞれ、有効と思われるアシル基を導入し、頭部の違うセラミドの合成に成功した。
• ポリエステル系ペプチドミミックを指向したVCDによるバイオポリマー立体構造解析法

  文部科学省科学研究費：基盤研究(B)

  研究期間 : 2015年04月 -2018年03月 

  代表者 : 門出 健次
• 理論計算を必要としない赤外円二色性スペクトルによる新規絶対配置決定法の開発

  文部科学省科学研究費：基盤研究(B)

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 門出 健次
• 先端融合領域イノベーション創出拠点の形成

  科学技術振興機構（文部科学省）：未来創薬・医薬イノベーション拠点形成

  研究期間 : 2006年 -2015年 

  代表者 : 山口 佳三
• フードイノベーション創造支援事業（札幌市補助事業）

  札幌市：実証研究支援補助金

  研究期間 : 2014年 

  代表者 : 門出 健次
• 赤外円二色法による迅速高次構造解析と三次元化合物ライブラリの構築

  日本学術振興会：科学研究費助成事業

  研究期間 : 2011年 -2013年 

  代表者 : 門出 健次, CHANNAPILLE Kopp

   

  本研究では、特別研究員のこれまでの合成技術により合成した化合物を合成し、立体化学研究をVCD法により遂行、新規キラルドラッグライク化合物ライブラリの構築することを目的としている。本年度は生理活性物質として、スフィンゴシンにしぼった。スフィンゴシンは、疎水性、親水性の両方性質をもつため取扱いが困難である。そのため、昨年に引き続きスフィンゴシン補足樹脂の合成と最適化を実施した。スフィンゴシン補足樹脂作成のため、グルタルアルデヒド誘導体の大量合成を実施した。また、樹脂に関しても複数種類を入手し、カップリングにより補足樹脂の最適化を試みたが、当面、従来法の樹脂が最適であるとの結論を得た。また、ファイトスフィンゴシンに対しても補足、リリースの最適化を行った。樹脂は、ファイトスフィンゴシン類に関しても有効であることが判明した。更に、多様性化合物の確保をめざして、天然資源からの簡便抽出法の開発を試みた。サンプルとして、タモギダケを選び、これからグルコセラミドを大量に単離、標準サンプルとした。糖鎖の加水分解を実施したが、反応の進行が困難であったので、詳細な加水分解の条件検討を実施した。また、別途合成されたスフィンゴシン誘導体を用いて、2位のアミノ基に対して、研究室保有のカルボン酸ライブラリのアミド化反応による多種類化合物の調整を試みた。特に、多種類のカルボン酸に対して、容易かつ確実に進行する条件を検討した。また、合成した光学活性生理活性物質に関して、単離することなく、プレート上での生理活性試験を実施した。脂質関係酵素を含む細胞系と蛍光ラベル基質を用いたアッセイ系での活性測定を試みた。その結果、一部について活性が認められた。
• 官能基特異的反応に着目したスフィンゴシン類の選択的捕捉法の開発

  文部科学省科学研究費：挑戦的萌芽研究

  研究期間 : 2011年 -2013年 

  代表者 : 門出 健次
• 赤外円二色性スペクトルによる分子キラル分析法の開発

  財団法人篷庵社：研究助成金

  研究期間 : 2010年 -2013年 

  代表者 : 門出 健次
• さっぽろバイオクラスター構想 ”Bio-S”

  文部科学省：知的クラスター創成事業（第II期）

  研究期間 : 2007年 -2011年 

  代表者 : 鈴木 文夫
• 赤外円二色法によるスタンダード・キロプティカル構造解析法の構築

  文部科学省科学研究費：基盤研究(B)

  研究期間 : 2008年 -2010年 

  代表者 : 門出 健次
• 生物によるキラル円偏光識別とその分子機構の解明

  文部科学省科学研究費：挑戦的萌芽研究

  研究期間 : 2008年 -2010年 

  代表者 : 門出 健次
• 疾患早期診断のための糖鎖自動分析装置開発

  科学技術振興機構（文部科学省）：先端計測分析技術機器・開発事業

  研究期間 : 2004年 -2008年 

  代表者 : 西村 紳一郎
• 弱い相互作用に着目した機能性天然物の高速探索

  文部科学省科学研究費：萌芽研究

  研究期間 : 2005年 -2007年 

  代表者 : 門出 健次
• 赤外領域円二色性スペクトルによるキラル分析法の応用研究

  文部科学省科学研究費：基盤研究(B)

  研究期間 : 2004年 -2007年 

  代表者 : 門出 健次
• 不凍糖タンパク質の生理機能を活用する臓器・細胞保存剤の開発

  経済産業省：地域コンソーシアム研究開発事業

  研究期間 : 2004年 -2005年 

  代表者 : 西村 紳一郎
• 可視光による脂質二分子膜を介したイオン輸送の光制御

  日本学術振興会：科学研究費助成事業

  研究期間 : 2003年 -2005年 

  代表者 : 神 隆, 門出 健次

   

  光に応答する脂質二分子膜は光電子デバイスや光増幅器を組み込んだ人工的な視覚システムとして非常に興味がもたれている。光に応答する二分子膜としては、従来、両親媒性のアゾベンゼンやスピロベンゾピランなどの光応答性化合物を含む脂質二分子膜がよく研究されてきた。このような膜の光応答性は、おもにドープされたクロモフォアーの光異性化による膜コンダクタンスの変化(膜構造の乱れ)に基づいている。一方、膜を介したイオン輸送の光制御に関する研究は、クロモフォアーを修飾したチャネルやキャリアーをドープした人工膜でおこなわれてきたが、そのほとんどは紫外光を用いたものである。紫外光の長時間照射は、光応答性膜を構成する脂質分子あるいはクロモフォアーにダメージ(光分解)をもたらす欠点がある。 本研究課題では、400nmより長い可視光に応答する人工キャリアーにより、脂質二分子膜を介したナトリウムイオン輸送の光制御に成功した。光応答性のキャリアー分子として、カリックス[4]アレーン分子にジメチルアミノアゾベンゼン誘導体を結合させたものを用いた。ジメチルアミノアゾベンゼンは、一般的なアゾベンゼンと異なり、400nm以上の可視部の光によってシスートランス互変異性を起すクロモフォアーであり、これを利用する事により可視光に応答するキャリアーの合成に成功した。本研究は、人工二分子膜系で可視光のみを利用してイオン輸送の制御をおこなったはじめての例であり、その成果は人工的な光応答性膜(視覚システム)の研究に重要な知見をあたえるもの考えられる。
• 糖鎖自動合成装置における反応モニタリング技術の開発

  経済産業省：糖鎖エンジニアリングプロジェクト/糖鎖構造解析技術開発

  研究期間 : 2003年 -2005年 

  代表者 : 西村 紳一郎
• 人工細胞外マトリックスの精密分子設計と靭帯および関節軟骨細胞再生への応用

  文部科学省科学研究費：基盤研究(B)

  研究期間 : 2003年 -2005年 

  代表者 : 眞島 任史
• 複合糖鎖データベースリーディングプロジェクト

  文部科学省：新世紀重点研究創成プラン（ＲＲ）

  研究期間 : 2003年 -2004年 

  代表者 : 西村 紳一郎
• 複合糖質の新規キラル分析法の開発

  文部科学省科学研究費：萌芽研究

  研究期間 : 2002年 -2004年 

  代表者 : 門出 健次
• 北方系植物資源データベースの構築及び抽出物ライブラリの整備

  国土交通省：一次産品活用型バイオベンチャー育成支援調査

  研究期間 : 2004年 

  代表者 : 門出 健次
• 機能性糖鎖複合材料創製技術開発

  経済産業省：大学連携産業科学技術研究開発プロジェクト

  研究期間 : 1999年 -2003年 

  代表者 : 西村 紳一郎
• CD励起子法の新しい展開:単一官能基をもつ天然有機化合物への新規応用戦略

  日本学術振興会：科学研究費助成事業

  研究期間 : 1999年 -2002年 

  代表者 : 原田 宣之, 松本 高利, 渡辺 政隆, 門出 健次

   

  1.我々は単一の官能基を有する天然有機化合物の絶対立体化学を励起子キラリティー法で決定する新規戦略の開発に成功した。現在、さらに計算の信頼性向上のための研究を推進している。 2.我々は、種々のラセミ体アルコールに不斉補助基のキラルカルボン酸を共有結合させてジアステレオマーエステルを得て、シリカゲルHPLCにより分離し、不斉補助基を切断し光学的に純粋なアルコールを得る方法の開発と種々の系への応用に成功した。この方法ではHPLCでジアステレオマーを明瞭に分離でき、得られた各ジアステレオマーは光学的に純粋であり、不斉補助基を切断して得られる化合物は光学純度100%である。 3.我々は絶対配置既知の不斉補助基chiral dichlorophthalic acidを内部標準として、X線結晶解析を行い問題部分の絶対配置を決定する方法の開発と応用に成功した。この場合、重原子を含む必要は無く、得られる結果は全く明瞭である。 4.さらに我々は最近、良く使用されるNMRの磁気異方性効果を用いた方法が適用できる理想的なキラルカルボン酸2-methoxy-2-(1-naphthyl)propionic acid(MαNP acid)の開発にも成功した。この方法は天然有機化合物の絶対構造研究に特に有用である。我々の開発したこの試薬は、Mosher試薬MTPAや、Trost試薬MPAなどよりも優れており、これらを凌駕している。 5.我々はさらにこのキラルカルボン酸MαNP acidが種々のアルコール類の不斉識別能力に優れ、光学分割に応用できることを明らかにした。 6.以上に挙げたキラルカルボン酸MαNP acidの特徴から我々は最近、1H NMRあるいはMSを用いた新しい鏡像体過剰決定法の開発にも成功した。
• コンピュータを用いた生物有機資源からの消化抑制剤等の開発

  経済産業省：即効型地域新生コンソーシアム研究開発事業

  研究期間 : 2002年 

  代表者 : 門出 健次
• 色覚に関与する視物質のモデル化合物による解析

  文部科学省科学研究費：奨励研究(A)

  研究期間 : 1999年 -2000年 

  代表者 : 門出 健次
• Pacifichem2000渡航費用

  栗林育英学術財団：

  研究期間 : 2000年 

  代表者 : 門出 健次
• フッ素ラベルリガンドとレセプターとの相互作用に関する研究

  文部省・科学研究費：奨励研究(A)

  研究期間 : 1997年 -1998年 

  代表者 : 門出 健次
• アブラナ科植物のファイトアレキシンの生成機構

  日本学術振興会：科学研究費助成事業

  研究期間 : 1994年 -1994年 

  代表者 : 高杉 光雄, 門出 健次

   

  1.アブラナ科植物のファイトアレキシンの産生を誘導する内因性エリシターの探索 カブを大根おろし状とし、おろし汁を除去、洗浄したカブ繊維状組織を滅菌水に懸濁し、紫外線を照射した後、水層に滲出してくる物質にエリシター活性を認めた。透析により分子量約1000以上の不活性部を除き、ファイトアレキシンcyclobrassininの生成量をエリシター活性の指標として各種クロマトグラフィーにより分離し、酸性糖質分画に活性を認めた。 2.cyclobrassinin生合成経路の検討 cyclobrassininがmethoxybrassininを経由するか、あるいはbrassininから直接生成するか検討した。重水素標識brassininを投与した後、単離したcyclobrassininとmethoxybrassininについて重水素標識の取り込を調査したところ、cyclobrassininには取り込まれたもののmethoxybrassininには全く取り込まれていなかった。また重水素標識methoxybrassininの投与により得たcyclobrassininにも重水素標識が全く取り込まれないことも確認した。従って、cyclobrassininはmethoxybrassininを経由しないで生合成される。 3.brassicanal Aの生合成研究 紫外線照射により活性化したカブスライスに、生体異物であるアセトアニリドを投与したところ、アセトアニリド由来のアニリンがbrassicanal Aの生合成中間体をトラップした構造の生成物を得た。これより、cyclobrassininより生成するdehydrobrassininの加水分解生成物、3-formyl-2-mercaptoindoleのメチル化によりbrassicanal Aが生合成されると推定した。
• シロイヌナズナのファイトアレキシン及びその生合成研究

  文部省・科学研究費：奨励研究(A)

  研究期間 : 1993年 

  代表者 : 門出 健次
• 18th IUPAC International Symposium on the Chemistry of Natural Products渡航費用

  実吉財団：

  研究期間 : 1992年 

  代表者 : 門出 健次
• アブラナ科植物ファイトアレキシンの生合成研究

  文部省・科学研究費：奨励研究(A)

  研究期間 : 1992年 

  代表者 : 門出 健次
• アブラナ科植物の産生する新規含硫ファイトアレキシンの生物有機化学的研究

  文部省・科学研究費：一般研究(B)

  研究期間 : 1988年 -1990年 

  代表者 : 高杉 光雄
• 電荷移動プロセスとひずみ結合の反応性

  文部省・科学研究費：一般研究(C)

  研究期間 : 1990年 

  代表者 : 平尾 健一
• ヒラタケ病原菌の生理活性物質に関する研究

  北海道大学：教育研究学内特別経費

  研究期間 : 1990年 

  代表者 : 門出 健次
• ヒラタケ病原細菌の生産する生理活性物質に関する生物有機化学的研究

  秋山記念生命科学振興財団：

  研究期間 : 1990年 

  代表者 : 門出 健次
• 17th IUPAC International Symposium on the Chemistry of Natural Products渡航費用

  薬学振興財団：

  研究期間 : 1990年 

  代表者 : 門出 健次
• 細菌感染により誘導されるキク科食用植物の抗菌活性物質の生物有機化学的研究

  文部省・科学研究費：奨励研究(A)

  研究期間 : 1989年 

  代表者 : 門出 健次
• Chiral analysis of glycoconjugates by Vibrational Circular Dichroism (VCD)

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• 2015年4月1日 - 2017年3月31日 大学院先端生命科学研究院副研究院長
• 2017年4月1日 - 2019年3月31日 大学院先端生命科学研究院副研究院長
• 2023年4月1日 - 2025年3月31日 大学院先端生命科学研究院副研究院長
• 2023年4月1日 - 2024年3月31日 総長補佐

委員歴

• 2020年07月 - 現在   蓬庵社   学術委員   任期：2022年6月30日まで
• 2019年05月 - 現在   分子不斉研究機構   理事
• 2015年 - 現在   キラル分光国際会議   委員
• 2010年 - 現在   日本糖質学会   日本糖質学会評議員   日本糖質学会
• 2009年07月 - 現在   シンポジュウム モレキュラー・キラリティー   実行委員会委員
• 2007年 - 現在   高分子学会   北海道支部幹事   高分子学会
• 2016年 - 2018年   高分子学会   北海道支部 支部長
• 2016年 - 2018年   高分子学会   理事
• 2013年 - 2018年   フルオラス科学研究会   理事
• 2013年 - 2015年   第１５回キラル分光国際会議（CD2015）   実行委員長
• 2008年 - 2010年   高分子学会   第59回高分子討論会 運営委員   高分子学会
• 2002年 - 2006年   高分子学会   会誌編集委員   高分子学会
• 2003年 - 2005年   高分子学会   日本高分子学会 討論会 実行委員   高分子学会