Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Advanced Life Science　Advanced Transdisciplinary Science　Chemical Biology

Affiliation (Master)

• Faculty of Advanced Life Science　Advanced Transdisciplinary Science　Chemical Biology

researchmap

Profile and Settings

Profile and Settings

• Name (Japanese)

  Taniguchi

• Name (Kana)

  Tohru

• Name

  200901079905724057

Achievement

Research Interests

• organic chemistry   physical chemistry   vibrational circular dichroism   circular dichroism   NMR calculation   Raman optical activity   chirality   The origin of life   biofunctional chemistry   natural product chemistry   

Research Areas

• Life sciences / Bioorganic chemistry

Research Experience

• 2023/08 - Today Hokkaido University Faculty of Advanced Life Science Associate Professor
• 2019/05 - 2023/07 Hokkaido University Faculty of Advanced Life Science
• 2010/05 - 2019/04 Hokkaido University Faculty of Advanced Life Science Assistant Professor
• 2008/08 - 2010/04 Harvard University Chemistry and Chemical Biology Department Postdoctoral Fellow
• 2007/05 - 2008/07 Columbia University Department of Chemistry Postdoctoral Fellow (JSPS)
• 2005/04 - 2007/03 日本学術振興会 特別研究員（DC2）
• 2005/08 - 2006/07 Columbia University Department of Chemistry Visiting Scholar

Education

• 2004/04 - 2007/03  Hokkaido University
• 2002/04 - 2004/03  Hokkaido University
• 1998/04 - 2002/03  Hokkaido University  School of Science  Biological Sciences

Awards

• 2020/01 Thieme Chemistry Journal: Thieme Chemistry Journals Award
  
• 2019/10 公益財団法人MSD生命科学財団： Chemist Award BCA
   「キラル分光学による溶液分子構造解析が拓く有機化学」
• 2015/05 Award for Encouragement of Research in Polymer Science
   受賞研究題目「赤外円二色分光法を用いた溶液中における高分子の構造解析」 

  受賞者: TANIGUCHI Tohruhttp://main.spsj.or.jp/c15/sho/shoran.php
• 2015/03 The Chemical Society of Japan Award for Young Chemists
   受賞研究題目「赤外円二色性による立体配置・立体配座決定法の開発」 

  受賞者: TANIGUCHI Tohruhttp://www.chemistry.or.jp/news/information/26-9.html
• 2013/03 Lecturer of Young Scholar Lecture Series, selected by The Chemical Society of Japan
   

  受賞者: TANIGUCHI Tohruhttp://www.csj.jp/nenkai/standing/young.html
• 2012/11 NOASTEC (Northern Advancement Center for Science & Technology) Presidential Prize
   

  受賞者: TANIGUCHI Tohruhttp://www.noastec.jp/topics/2012/11/post-87.html
• 2012/09 Incentive Award at 54th Symposium on the Chemistry of Natural Products
   

  受賞者: TANIGUCHI Tohruhttp://www.tennenyuuki.ne.jp/index.html
• 2012/07 Young Scientist’s Research Award in Natural Product Chemistry at the 47th Natural Product Chemistry Meeting
   

  受賞者: TANIGUCHI Tohruhttp://ndk.dip.jp/~shashin/danwa/award-past.html
• 2009/06 Participant of the 59th Meeting of Nobel Prize Winners in Chemistry at Lindau, selected by JSPS
   

  受賞者: TANIGUCHI Tohruhttp://www.jsps.go.jp/j-lindau/koe2.html
• 2009/01 Uehara Memorial Foundation Postdoctoral Research Fellow
   

  受賞者: TANIGUCHI Tohru
• 2007/07 Travel Award by the Stereochemical Society of Greater New York for the poster presentation at 19th International Symposium on Chirality
   

  受賞者: TANIGUCHI Tohru
• 2007/05 JSPS postdoctoral fellow for research abroad
   

  受賞者: TANIGUCHI Tohru
• 2007/04 日本学術振興会 特別研究員（PD）（海外特別研究員採用のため辞退）
   

  受賞者: 谷口 透
• 2005/08 Best Poster Award (1st Place), 10th International Conference on Circular Dichroism
   

  受賞者: TANIGUCHI Tohru
• 2005/04 日本学術振興会 特別研究員（DC2）
   

  受賞者: 谷口 透
• 2004/04 YKK大学院博士学生給与奨学金（吉田育英会ドクター21）1期生
   

  受賞者: 谷口 透
• 2002/04 YKK大学院修士学生給与奨学金（吉田育英会マスター21）
   

  受賞者: 谷口 透

Published Papers

• Raman optical activity study of deuterated sugars: deuterium labelling as a tool for structural analysis.

  Tohru Taniguchi, Davidson Obinna Agbo, Qin Yang, Josef Kapitán, Tao Wu, Shuki Oyama, Shuji Akai, Yoshinari Sawama, Petr Bouř

  Physical chemistry chemical physics : PCCP 26 (32) 21568 - 21574 2024/08/14 

  Structural analyses using Raman optical activity (ROA) spectroscopy conventionally rely on vibrational signals in the fingerprint region ranging from 100 to 1800 cm-1. Use of deuterium labelling to observe ROA signals in the C-D stretching region provides additional information about a local structure of large molecular systems. So far, the potential of C-D stretching ROA signals for structural analysis has rarely been explored. In the present work, we synthesized model deuterated glucose monosaccharides and studied their ROA properties by employing molecular dynamics and density functional theory to interpret the spectra. A good agreement between the simulated and experimental spectra is achieved when the proper conformer ratios are considered. This shows the usefulness of ROA spectroscopy assisted by deuterium labelling for stereochemical and conformational analysis.
• Computational Study on the Conformational Flexibility-Mediated Intramolecular Oxidative Spirocyclization of Procyanidin B4.

  Haruka Kataoka, Yuya Kakumu, Davidson Obinna Agbo, Tohru Taniguchi, Emiko Yanase

  The Journal of organic chemistry 2024/08/09 

  Procyanidins, found widely in foods and beverages, are prone to oxidation, yet the chemical structures of their oxidation products and the mechanisms involved remain unclear. Herein, we report that the conformation of procyanidin B4 influences its oxidation products and their stereochemistry. Eight spirocyclized oxidation products were obtained from procyanidin B4 and classified as S- or R-forms based on the configuration of the spiro carbons. The ratios of S- and R-forms derived from the compact and extended rotamers of procyanidin B4, respectively, varied with the solvent. DFT calculations suggested that the four lowest-energy conformers of procyanidin B4 are diverged by interflavan bond rotation and heterocyclic ring inversion. Conformations with an axial-oriented B-ring were estimated as reactive conformations showing proximity between reaction sites on the B- and D-rings. Moreover, the extended rotamer bearing the axially oriented B-ring showed greater stabilization by noncovalent interactions (NCIs), such as OH-π interactions, compared to the counterpart of the compact rotamer. This NCI-based stabilization accounts for a higher production of the R-form despite the predominant presence of the compact rotamer in H2O. These findings highlight the conformational effects that bias the stereoselectivity of oxidative spirocyclization in procyanidin B4, advancing our understanding of procyanidin oxidation mechanisms and product stereochemistry.
• 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 87 1358 - 1369 2024/04/24 

  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.
• Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

  Ryuichi Sakai, Ken Matsumura, Hajime Uchimasu, Kei Miyako, Tohru Taniguchi, V Raghavendra Rao Kovvuri, Anjana Delpe Acharige, Kenneth G Hull, Daniel Romo, Lakkana Thaveepornkul, Sarin Chimnaronk, Hiroko Miyamoto, Ayato Takada, Hiromi Watari, Masaki J Fujita, Jiro Sakaue

  The Journal of organic chemistry 89 5977 - 5987 2024/04/01 [Refereed]
   

  Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).
• 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 Chem. 1755-4330 2024/02/28
• Structural-model-based genome mining can efficiently discover novel non-canonical terpene synthases hidden in genomes of diverse species

  Tohru Abe, Haruna Shiratori, Kosuke Kashiwazaki, Kazuma Hiasa, Daijiro Ueda, Tohru Taniguchi, Hajime Sato, Takashi Abe, Tsutomu Sato

  Chemical Science 15 10402 - 10407 2041-6520 2024 [Refereed]
   

  Non-canonical terpene synthases with primary sequences that are unrecognizable as canonical terpene synthases could be discovered through structural-model-based genome mining.
• Amoxetamide A, a new anoikis inducer, produced by combined-culture of Amycolatopsis sp. and Tsukamurella pulmonis

  Chengqian Pan, Hiroaki Ikeda, Mayuri Minote, Tensei Tokuda, Takefumi Kuranaga, Tohru Taniguchi, Naoya Shinzato, Hiroyasu Onaka, Hideaki Kakeya

  The Journal of Antibiotics 77 (1) 66 - 70 0021-8820 2023/10/30
• Vibrational circular dichroism spectroscopy in the C–D, X≡Y, and X=Y=Z stretching region

  Tohru Taniguchi, Davidson Obinna Agbo

  Physical Chemistry Chemical Physics 25 (42) 28567 - 28575 1463-9076 2023/10 [Refereed][Invited]
   

  VCD spectroscopy in the 1900–2400 cm⁻¹ region has less often been studied. This article briefly summarises VCD studies in this spectral region and discusses the properties of 1900–2400 cm⁻¹ chromophores.
• スペクトル理論計算を用いた構造解析の注意点

  谷口透

  有機合成化学協会誌 2023/09 [Refereed][Invited]
  
• Vibrational Circular Dichroism Studies on Axially Chiral Carbodiimides and Allenes

  Tohru Taniguchi

  Synlett 34 (16) 1839 - 1844 0936-5214 2023/04/11 [Refereed][Invited]
   

  Abstract The axial chirality of molecules with two consecutive double bonds (X=Y=Z) has not been well studied because of a lack of analytical methods and because of difficulties in their preparation in enantiomerically pure forms. This Synpacts article describes the use of vibrational circular dichroism spectroscopy to study the stereochemistry of carbodiimides and allenes. A strategy to obtain carbodiimides with one-handed chirality by using conformationally restrained frameworks is also discussed. 1 Introduction 2 Carbodiimides with Partially Biased Axial Chirality and One-Handed Axial Chirality 3 Axially Chiral Allenes 4 Conclusions
• 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 29 e202203396  0947-6539 2023/02/07 [Refereed][Not invited]
  
• Scope and limitations of absolute configuration determination of allenic natural products using the C=C=C stretching VCD signal.

  Tohru Taniguchi, Mutmainah, Shu Takimoto, Takahiro Suzuki, Soichiro Watanabe, Fuyuhiko Matsuda, Taiki Umezawa, Kenji Monde

  Organic & biomolecular chemistry 21 (3) 569 - 574 2023/01/18 [Refereed][Not invited]
   

  The allene functional group in natural products isolated so far exists in a non-racemic form, but its axial chirality is difficult to elucidate. Allenes exhibit a characteristic antisymmetric CCC stretching mode at around 1950 cm-1, and their VCD properties have not been studied in detail. This work, for the first time, applied VCD spectroscopy to allenic natural products and allenic molecules with other asymmetric centers focusing on the antisymmetric CCC stretching mode. This vibrational mode yielded a negligibly weak VCD signal for several molecules, but in the presence of electron-withdrawing and/or conjugating substituents, it generated a stronger one. Its sign was found to be influenced by the nature of substituents. These findings should deepen the understanding of the VCD properties of the allene functional group and should be useful for future studies of chiral allenes.
• 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 1523-7060 2022/10/03 [Refereed][Not invited]
  
• 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 1359-7345 2022/04 [Refereed][Not invited]
   

  Using VCD spectroscopy to elucidate absolute configuration and conformational preferences of hydroxy fatty acids, lipid epoxides, and lipid hydroperoxides.
• 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 1523-7060 2022/03/11 [Refereed][Not invited]
  
• 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 1477-0520 2022/01 [Refereed][Not invited]
   

  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 2193-5807 2021/10/18 [Refereed][Not invited]
  
• 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 0947-6539 2021/10/11 [Refereed][Not invited]
  
• Myrindole A, an Antimicrobial Bis-indole from a Marine Sponge Myrmekioderma sp.

  Philipp Moosmann, Tohru Taniguchi, Kazuo Furihata, Hiroaki Utsumi, Yuji Ise, Yasuhiro Morii, Nobuhiro Yamawaki, Tomohiro Takatani, Osamu Arakawa, Shigeru Okada, Shigeki Matsunaga

  Organic Letters 23 (9) 3477 - 3480 1523-7060 2021/05/07 [Refereed][Not invited]
   

  Myrindole A, a bis-indole alkaloid, was isolated from the deep-sea sponge Myrmekioderma sp. The high degree of unsaturation of the molecule complicated the assignment of its structure by standard 2D-NMR experiments but was ultimately achieved by a combination of 1H-15N-HMBC and 1,n-ADEQUATE experiments as well as the comparison of measured and calculated CD spectra. Myrindole A showed antimicrobial activity against Gram-positive and Gram-negative bacteria.
• 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 1463-9076 2021 [Refereed]
   

  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.
• Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

  Yohei Morishita, Yu Aoki, Mei Ito, Daisuke Hagiwara, Kensho Torimaru, Daichi Morita, Teruo Kuroda, Hanako Fukano, Yoshihiko Hoshino, Masato Suzuki, Tohru Taniguchi, Keiji Mori, Teigo Asai

  Organic Letters 1523-7060 2020/07/14 [Refereed][Not invited]
  
• Structural Studies on Stilbene Oligomers Isolated from the Seeds of Melinjo (Gnetum gnemon L.)

  Hiroko Tani, Hiroyuki Koshino, Tohru Taniguchi, Maiko Yoshimatsu, Susumu Hikami, Shunya Takahashi

  ACS Omega 5 (21) 12245 - 12250 2470-1343 2020/06/02 [Refereed][Not invited]
  
• Total Synthesis of Sophoraflavanone H and Confirmation of Its Absolute Configuration

  Haruka Murakami, Tomohiro Asakawa, Yoshihiro Muramatsu, Ryo Ishikawa, Aiki Hiza, Yuta Tsukaguchi, Yohei Tokumaru, Masahiro Egi, Makoto Inai, Hitoshi Ouchi, Fumihiko Yoshimura, Tohru Taniguchi, Yoshinobu Ishikawa, Mitsuru Kondo, Toshiyuki Kan

  Organic Letters 22 (10) 3820 - 3824 1523-7060 2020/05/15 [Refereed][Not invited]
  
• Synthetic-biology-based discovery of a fungal macrolide from Macrophomina phaseolina.

  Yohei Morishita, Terutaka Sonohara, Tohru Taniguchi, Kiyohiro Adachi, Makoto Fujita, Teigo Asai

  Organic & biomolecular chemistry 18 (15) 2813 - 2816 2020/04/15 [Refereed][Not invited]
   

  A synthetic biology approach based on genome mining and heterologous biosynthesis is a powerful tool for discovering novel natural products from a tremendous gene resource. We carried out fungal genome mining guided by a polyketide synthase gene using a public database and found a putative macrolide biosynthetic gene cluster with a highly reducing polyketide synthase gene and a thioesterase gene in Macrophomina phaseolina. Reconstitution of the cluster in Aspergillus oryzae, a model heterologous host for fungal natural product biosynthesis, produced a new 12-membered macrolide, phaseolide A. The absolute stereochemistry was elucidated by vibrational circular dichroism spectroscopy and the crystalline sponge method.
• Correction: Synthetic-biology-based discovery of a fungal macrolide from Macrophomina phaseolina

  Yohei Morishita, Terutaka Sonohara, Tohru Taniguchi, Kiyohiro Adachi, Makoto Fujita, Teigo Asai

  Organic & Biomolecular Chemistry 18 (17) 3392 - 3392 1477-0520 2020 

  Correction for ‘Synthetic-biology-based discovery of a fungal macrolide from Macrophomina phaseolina’ by Yohei Morishita et al., Org. Biomol. Chem., 2020, DOI: 10.1039/d0ob00519c.

• 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 0947-6539 2020 [Refereed][Not invited]
  
• 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 Lett. 60 150917  2019/10 [Refereed][Not invited]
  
• Post-genomic approach based discovery of alkylresorcinols from a cricket-associated fungus; Penicillium soppi.

  Akiho Kaneko, Yohei Morishita, Kento Tsukada, Tohru Taniguchi, Teigo Asai

  Org. Biomol. Chem. 17 5239 - 5243 2019/08 [Refereed][Not invited]
  
• The Discovery of Fungal Polyene Macrolides via a Postgenomic Approach Reveals a Polyketide Macrocyclization by trans-Acting Thioesterase in Fungi.

  Yohei Morishita, Huiping Zhang, Tohru Taniguchi, Keiji Mori, Teigo Asai

  Organic letters 21 (12) 4788 - 4792 2019/06/21 [Refereed][Not invited]
   

  Heterologous expression of a unique biosynthetic gene cluster (BGC) comprising a highly reducing polyketide synthase and stand-alone thioesterase genes in Aspergillus oryzae enabled us to isolate a novel 34-membered polyene macrolide, phaeospelide A (1). This is the first isolation of a fungal polyene macrolide and the first demonstration of fungal aliphatic macrolide biosynthetic machinery. In addition, sequence similarity network analysis demonstrated the existence of a large number of BGCs for novel fungal macrolides.
• Use of plant hormones to activate silent polyketide biosynthetic pathways in Arthrinium sacchari, a fungus isolated from a spider

  Yohei Morishita, Yusuke Okazaki, Yi Yi Luo, Jun Nunoki, Tohru Taniguchi, Yoshiteru Oshima, Teigo Asai

  Organic & Biomolecular Chemistry 17 (4) 780 - 784 1477-0520 2019 [Refereed][Not invited]
   

  A new method to activate fungal silent biosynthesis by using natural and synthetic plant hormones.

• Determination of the Absolute Configurations and Sensory Properties of the Enantiomers of a Homologous Series (C6-C10) of 2-Mercapto-4-alkanones

  Christiane Kiske, Anja Devenie Riegel, Ronja Hopf, Anna Kvindt, Iulia Poplacean, Tohru Taniguchi, Mahadeva M. M. Swamy, Kenji Monde, Wolfgang Eisenreich, Karl-Heinz Engel

  J. Agric. Food Chem. 67 1187 - 1196 2019/01 [Refereed][Not invited]
  
• Preparation of Carbodiimides with One-Handed Axial Chirality.

  Tohru Taniguchi, Takahiro Suzuki, Haruka Satoh, Yukatsu Shichibu, Katsuaki Konishi, Kenji Monde

  J. Am. Chem. Soc. 140 15577 - 15581 2018/11 [Refereed][Not invited]
  
• Synthesis and Photochemical Properties of Axially Chiral Bis(dinaphthofuran)

  Chiaki Katakami, Shogo Kamo, Ayame Torii, Nobuyuki Hara, Yoshitane Imai, Tohru Taniguchi, Kenji Monde, Yusuke Okabayashi, Takuya Hosokai, Kouji Kuramochi, Kazunori Tsubaki

  J. Org. Chem. 133 14610 - 14616 2018/10 [Refereed][Not invited]
  
• Palladium-Catalyzed Asymmetric C(sp3)-H Allylation of 2-Alkylpyridines

  Ryo Murakami, Kentaro Sano, Tomohiro Iwai, Tohru Taniguchi, Kenji Monde

  Angew. Chem. Int. Ed. 57 9465 - 9469 2018/06 [Refereed][Not invited]
  
• Enantio- and Diastereoselective Synthesis of Latanoprost using an Organocatalyst

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

  Chem. Eur. J. 24 8409 - 8414 2018/06 [Refereed][Not invited]
  
• KB343, a Cyclic Tris-guanidine Alkaloid from Palauan Zoantharian Epizoanthus illoricatus

  Ken Matsumura, Tohru Taniguchi, James D. Reimer, Shuntaro Noguchi, Masaki J. Fujita, Ryuichi Sakai

  Organic Letters 20 (10) 3039 - 3043 1523-7052 2018/05/18 [Refereed][Not invited]
   

  A new tris-guanidine alkaloid, KB343 (1), was isolated from the aqueous extract of a Palauan zoantharian, Epizoanthus illoricatus. The structure of 1 was determined on the basis of spectral analyses of 1 and its derivatives. The absolute configuration for 1 was determined upon comparison of the CD spectrum of 1 to those obtained from density functional theory calculations. The structure of 1 is highly unusual, as three guanidine groups are present in one ring system.
• Modifying oligoalanine conformation by replacement of amide to ester linkage

  Takahiro Hongen, Tohru Taniguchi, Kenji Monde

  Chirality 30 (4) 396 - 401 1520-636X 2018/04/01 [Refereed][Not invited]
   

  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.
• 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 1523-7060 2017/12 [Refereed][Not invited]
   

  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.
• Analysis of Molecular Configuration and Conformation by (Electronic and) Vibrational Circular Dichroism: Theoretical Calculation and Exciton Chirality Method

  Tohru Taniguchi

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 90 (9) 1005 - 1016 0009-2673 2017/09 [Refereed][Invited]
   

  The configuration and conformation of a molecule affect its bioactivity, reactivity, physical properties, etc., but the analysis of such stereostructures is often difficult and time-consuming. Having envisioned the usefulness of VCD (vibrational circular dichroism) spectroscopy and theoretical VCD/ECD (electronic circular dichroism) calculations in the field of natural product chemistry, the author has applied these techniques to various natural products and other organic molecules. This account describes the author's studies on molecular structural analysis by means of VCD/ECD theoretical calculations as well as exciton chirality methods. Advantages and limitations of these techniques are also briefly discussed.
• Asymmetric Synthesis of beta-Lactams through Copper-Catalyzed Alkyne-Nitrone Coupling with a Prolinol-Phosphine Chiral Ligand

  Yurie Takayama, Takaoki Ishii, Hirohisa Ohmiya, Tomohiro Iwai, Martin C. Schwarzer, Seiji Mori, Tohru Taniguchi, Kenji Monde, Masaya Sawamura

  CHEMISTRY-A EUROPEAN JOURNAL 23 (35) 8400 - 8404 0947-6539 2017/06 [Refereed][Not invited]
   

  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 0037-9980 2017/05 [Refereed][Not invited]
   

  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

  Ji-Rong Huang, Muhammad Sohail, Tohru Taniguchi, Kenji Monde, Fujie Tanaka

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56 (21) 5853 - 5857 1433-7851 2017/05 [Refereed][Not invited]
   

  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.
• 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 1523-7060 2017/01 [Refereed][Not invited]
   

  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.
• alpha-Arylation of alpha-Amino Acid Derivatives with Arynes via Memory of Chirality: Asymmetric Synthesis of Benzocyclobutenones with Tetrasubstituted Carbon

  Koji Kasamatsu, Tomoyuki Yoshimura, Attila Mandi, Tohru Taniguchi, Kenji Monde, Takumi Furuta, Takeo Kawabata

  ORGANIC LETTERS 19 (2) 352 - 355 1523-7060 2017/01 [Refereed][Not invited]
   

  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 beta-Mercaptoalkanones Using Vibrational Circular Dichroism and H-1 NMR Analysis

  Christiane Kiske, Svenja Noerenberg, Miriam Ecker, Xingyue Ma, Tohru Taniguchi, Kenji Monde, Wolfgang Eisenreich, Karl-Heinz Engel

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 64 (45) 8563 - 8571 0021-8561 2016/11 [Refereed][Not invited]
   

  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.
• Enantioselective Total Synthesis of (+)-Hinckdentine A via a Catalytic Dearomatization Approach

  Kazuya Douki, Hiroyuki Ono, Tohru Taniguchi, Jun Shimokawa, Masato Kitamura, Tohru Fukuyama

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 138 (44) 14578 - 14581 0002-7863 2016/11 [Refereed][Not invited]
   

  Optically pure hinckdentine A was synthesized on a 300 mg scale via an asymmetric catalysis-based strategy. The key steps to the first asymmetric synthesis involved (i) enantioselective dearomative cyclization of an achiral N-acyl indole that allowed for the efficient construction of the key polycyclic indoline intermediate with a crucial tetrasubstituted stereogenic carbon center, (ii) Beckmann fragmentation-mediated ring expansion, (iii) rearrangement-based introduction of an anilinic nitrogen atom, (iv) regioselective tribromination, and (v) final closure of the cyclic amidine moiety.
• Asymmetric Diels-Alder Reaction of -Substituted and ,-Disubstituted ,-Enals via Diarylprolinol Silyl Ether for the Construction of All-Carbon Quaternary Stereocenters

  Yujiro Hayashi, Bojan P. Bondzic, Tatsuya Yamazaki, Yogesh Gupta, Shin Ogasawara, Tohru Taniguchi, Kenji Monde

  CHEMISTRY-A EUROPEAN JOURNAL 22 (44) 15874 - 15880 0947-6539 2016/10 [Refereed][Not invited]
   

  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 0032-3896 2016/09 [Refereed][Invited]
   

  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.
• 鏡の国の核酸医薬？ D-microRNAを標的とするL-RNAアプタマー

  谷口 透

  化学 71 (8) 59 - 60 2016/08 [Not refereed][Invited]
  
• A Bioinspired Synthesis of (+/-)-Rubrobramide, (+/-)-Flavipucine, and (+/-)-Isoflavipucine

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

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 55 (33) 9553 - 9556 1433-7851 2016/08 [Refereed][Not invited]
   

  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 0899-0042 2016/07 [Refereed][Not invited]
   

  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 0899-0042 2016/06 [Refereed][Not invited]
   

  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.
• VCD exciton chirality method

  門出健次, 谷口透

  分光研究 日本分光学会 65 (2) 137 - 144 0038-7002 2016/03 [Refereed][Invited]
  
• 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 1434-193X 2016/03 [Refereed][Not invited]
   

  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 1523-7060 2016/02 [Refereed][Not invited]
   

  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.
• Hydrogen bonding to carbonyl oxygen of nitrogen-pyramidalized amide - detection of pyramidalization direction preference by vibrational circular dichroism spectroscopy

  Siyuan Wang, Tohru Taniguchi, Kenji Monde, Masatoshi Kawahata, Kentaro Yamaguchi, Yuko Otani, Tomohiko Ohwada

  CHEMICAL COMMUNICATIONS 52 (21) 4018 - 4021 1359-7345 2016 [Refereed][Not invited]
   

  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 1477-0520 2016 [Refereed][Not invited]
   

  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.
• 3D-Structural Analysis of Polymers in Solution by Vibrational Circular Dichroism.

  Tohru Taniguchi

  Polymers 65 287  2016 [Not refereed][Invited]
  
• 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 0002-7863 2015/09 [Refereed][Not invited]
   

  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 0002-7863 2015/09 [Refereed][Not invited]
   

  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 alpha-Substituted alpha,beta-Enals Catalyzed by Diphenylprolinol Silyl Ether for the Construction of All-Carbon Quaternary Stereogenic Centers

  Yujiro Hayashi, Tatsuya Yamazaki, Yuki Nakanishi, Tsuyoshi Ono, Tohru Taniguchi, Kenji Monde, Tadafumi Uchimaru

  EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2015 (26) 5747 - 5754 1434-193X 2015/09 [Refereed][Not invited]
   

  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.
• Elucidating the 3D Structure of Natural Products by Vibrational Circular Dichroism.

  Tohru Taniguchi

  Chemistry Today 531 34 - 35 2015/06 [Not refereed][Not invited]
  
• Vibrational CD (VCD) Spectroscopy as a Powerful Toof for Chiral Analysis of Flavor Compounds.

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

  ACS Symp. Ser. 1212 35 - 56 2015 [Refereed][Invited]
  
• Revision of the relative and absolute stereochemistries of 3-hydroxydehydroiso-alpha-lapachone and its 8-hydroxy derivative

  Poonam Khandelwal, Pahup Singh, Tohru Taniguchi, Kenji Monde, Kohei Johmoto, Hidehiro Uekusa, Hironori Masubuti, Yoshinori Fujimoto

  PHYTOCHEMISTRY LETTERS 10 224 - 229 1874-3900 2014/12 [Refereed][Not invited]
   

  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.
• 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 0024-9297 2014/08 [Refereed][Not invited]
   

  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 0385-5414 2014/03 [Refereed][Not invited]
   

  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 1523-7060 2014/03 [Refereed][Not invited]
   

  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.
• Easy Access to Molecular Stereostructure in Solution – Vibrational Circular Dichroism.

  Tohru Taniguchi

  Chemistry Today 東京化学同人 518 (518) 47 - 51 0386-961X 2014 [Not refereed][Not invited]
  
• 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 1523-7060 2013/09 [Refereed][Not invited]
   

  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 1523-7060 2013/07 [Refereed][Not invited]
   

  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 0040-4039 2013/06 [Refereed][Not invited]
   

  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 (公社)日本薬学会 133年会 (2) 177 - 177 0918-9823 2013/03 [Refereed][Not invited]
  
• Structural Analysis of Chiral Molecules by Vibrational Circular Dichroism.

  Tohru Taniguchi

  Chemistry and Chemical Industry 66 825 - 826 2013 [Not refereed][Not invited]
  
• 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 1523-7060 2012/11 [Refereed][Not invited]
   

  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.
• 2 The VCD Exciton Chirality Method : A Novel Nonempirical Method for Determination of Absolute Configuration(Oral Presentation)

  Taniguchi Tohru, Manai Daisuke, Fukuzawa Masumi, Monde Kenji

  Symposium on the Chemistry of Natural Products, symposium papers 天然有機化合物討論会 (54) 7 - 12 2012/09/01 

  The determination of absolute configuration of chiral molecules is an essential but difficult step in natural product chemistry. Chiroptical spectroscopy is the sole technique that can nonempirically determine molecular chirality without need of crystallization. One of the most widely used is the exciton chirality method in electronic circular dichroism (ECD), developed by Harada and Nakanishi, but the requirement for two or more appropriate UV-vis chromophores restricts its applicability. Meanwhile, vibrational circular dichroism (VCD) spectroscopy using theoretical calculation has been a recent trend for its reliability and convenience; however, this approach has been hampered by the low sensitivity of vibrational absorption and the computational demand. In exploration of a more universal, sensitive method, we envisioned the potential of an exciton coupling approach in VCD. To test its feasibility, we synthesized various mono- and biscarbonyl chiral compounds and examined their VCD spectra. All the biscarbonyl compounds exhibited a bisignate VCD coupling whose intensity was 〜20 times higher than that of monocarbonyl compounds as a result of an interaction of two carbonyl groups. Furthermore, the signs of these couplets are consistent with the absolute twist of the two C=O bonds, which proved the reliability of "the VCD exciton chirality method" for determination of absolute configuration. Not only can the VCD exciton chirality method be used as conveniently as the ECD exciton chirality method, but also it can analyze molecules that are outside of the coverage of ECD and other spectroscopic techniques. In this study, we demonstrated the applicability of the VCD approach to various types of molecules such as spirobiscarbonyl compounds, α-amidelactam, α-acyloxyketone, and α-hydroxyketone. Furthermore, we recently revealed that this method can elucidate the chirality of diacylglycerolipids, major components of cell membrane. There have been few methods to analyze the absolute configuration of glycerolipids, but our current approach should provide new insight into evolution, and also clarify the detailed relationship between their chirality and biological functions. Last, the VCD exciton approach can be used as a signal intensifier. In some cases, less than 20 μg of analyte was sufficient to observe a VCD couplet, by which one can determine its absolute configuration. This method should find various usages in future, e.g., analysis of minuscule molecules with or without using theoretical calculation or time-resolved VCD measurement.
• 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 0040-4039 2012/04 [Refereed][Not invited]
   

  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.
• Optical Rotation, Electronic Circular Dichroism, and Vibrational Circular Dichroism of Carbohydrates and Glycoconjugates

  Tohru Taniguchi, Kenji Monde

  Comprehensive Chiroptical Spectroscopy 2 795 - 818 2012/02/17 [Refereed][Not invited]
  
• Exciton Chirality Method in Vibrational Circular Dichroism

  Tohru Taniguchi, Kenji Monde

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 (8) 3695 - 3698 0002-7863 2012/02 [Refereed][Not invited]
   

  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.
• Circular Dichroism Spectroscopy*Dedicated to Professor Koji Nakanishi on the occasion of his 85th birthday.

  Tohru Taniguchi, Toyonobu Usuki

  Supramolecular Chemistry 2012/01/27 

  Abstract Circular dichroism (CD) spectroscopy has been a powerful technique in the structural analysis of various chiral supramolecular systems. In order to obtain correct structural information it is essential to understand the basic concepts of CD, to optimize the measurement condition, and to properly interpret the data. This chapter addresses the following topics in order for the readers to use CD spectroscopy more efficiently: (i) the fundamental principles of CD spectroscopy and the technical point of the measurements; (ii) the exciton chirality method and its use in the configurational and conformational analysis of supermolecules; (iii) the introduction of basic concepts of induced CD; and (iv) the recent developments of computational simulation of CD spectra. We show that these basic concepts are applicable to the interpretation of CD data of further complicated supramolecular systems, by showing examples of a broad range of chiral supermolecules such as host‐guest systems, mechanically interlocked molecules, molecular machines, foldamer, polymers, and self‐assembled molecules. This chapter also briefly introduces the applications of a newly emerged CD (vibrational circular dichroism (VCD) spectroscopy) to supermolecules.
• Supramolecular Chemistry: from Molecules to Nanomaterials

  Tohru Taniguchi, Toyonobu Usuki

  Supramolecular Chemistry: from Molecules to Nanomaterials 2 393 - 410 2012 [Refereed][Not invited]
  
• Stereochemical Study of Chiral Tautomeric Furanones by Vibrational Circular Dichroism

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

  Symposium on the Chemistry of Natural Products, symposium papers 天然有機化合物討論会 (52) 163 - 168 2010/09/01 

  The naturally occurring furanones represented by furaneol^[○!R] (1), mesifuran (2) and homofuraneol (4a or 4b) are major flavor coponents in numerous fruits such as pineapples and strawberries. They have also been found in a range of cooked foodstuff as pleasant odor components that are generated mainly by heating sugars. These furanones are known to play an important role in flavor because of their extrelemy low threshold values and their burnt sugar odor charactristics. Since the discovery of these important aroma chemicals, large quantities have been utilized as raw materials in the flavor and fragrance industry, with worldwide annual consumption of up to almost 100t. These flavor-related furanones are believed to be biosynthesized via a glycoside from 6-deoxy-L-mannose in plants. However, most of such franones were isolated as optically inactive compounds due to their unique keto-enol tautomeric structures causing racemization. Furthermore, the keto-enol tautomeric structure has obstructed their derivatization toward an X-ray crystallographic study and a standard Mosher method, which has made any attempts to elucidate the relationship between their absolute configurations and odor unsuccessful. We have applied the vibrational circular dichroism (VCD) technique to these furanones. VCD is an emerging technique for stereochemical analyses in the field of life sciences as well as material sciences. We report the determination of the absolute configurations of these unique molecules and their chirality-dependent odor characteristics, which have remained unclear for the past 40 years since their isolation.
• Enantioselective Synthesis of 3,4-Chromanediones via Asymmetric Rearrangement of 3-Allyloxyflavones

  Jean-Charles Marie, Yuan Xiong, Geanna K. Min, Adam R. Yeager, Tohru Taniguchi, Nina Berova, Scott E. Schaus, John A. Porco

  JOURNAL OF ORGANIC CHEMISTRY 75 (13) 4584 - 4590 0022-3263 2010/07 [Refereed][Not invited]
   

  Asymmetric scandium(III)-catalyzed rearrangement of 3-allyloxyflavones was utilized to prepare chiral, nonracemic 3,4-chromanediones in high yields and enantioselectivities. These synthetic intermediates have been further elaborated to novel heterocyclic frameworks including angular pyrazines and dihydropyrazines. The absolute configuration of rearrangement products was initially determined by a nonempirical analysis of circular dichroism (CD) using time-dependent density functional theory (TDDFT) calculations and verified by X-ray crystallography of a hydrazone derivative. Initial studies of the mechanism support an intramolecular rearrangement pathway that may proceed through a benzopyrylium intermediate.
• Studying a Cell Division Amidase Using Defined Peptidoglycan Substrates

  Tania J. Lupoli, Tohru Taniguchi, Tsung-Shing Wang, Deborah L. Perlstein, Suzanne Walker, Daniel E. Kahne

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131 (51) 18230 - + 0002-7863 2009/12 [Refereed][Not invited]
   

  Three periplasmic N-acetylmuramoyl-L-alanine amidases are critical for hydrolysis of septal, peptidoglycan, which enables cell separation. The amidases cleave the amide bond between the lactyl group of muramic acid and the amino group of L-alanine to release a peptide moiety. Cell division amidases remain largely uncharacterized because substrates suitable for studying them have not been available. Here we have used synthetic peptidoglycan fragments of defined composition to characterize the catalytic activity and substrate specificity of the important Escherichia coli cell division amidase AmiA. We show that AmiA is a zinc metalloprotease that requires at least a tetrasaccharide glycopeptide substrate for cleavage. The approach outlined here can be applied to many other cell wall hydrolases and should enable more detailed studies of accessory proteins proposed to regulate amidase activity in cells.
• 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 0163-3864 2009/03 [Refereed][Not invited]
   

  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.
• Circular Dichroism (CD) for Natural Products

  Tohru Taniguchi, Koji Nakanishi

  Wiley Encyclopedia of Chemical Biology 3 (3) 368 - 378 2009 [Refereed][Not invited]
  
• P-5 Theoretical Calculation of Optical Activity : Absolute Configurations of Phytoalexins and Other Natural Products(Poster Presentation)

  Taniguchi Tohru, Monde Kenji, Schlingmann Gerhard, Nakanishi Koji, Berova Nina

  Symposium on the Chemistry of Natural Products, symposium papers 天然有機化合物討論会 (50) 281 - 284 2008/09/01
• 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 0899-0042 2008/03 [Refereed][Not invited]
   

  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.
• 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 1477-0520 2008 [Refereed][Not invited]
   

  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.
• Stereochemical studies of sialic acid derivatives by vibrational circular dichroism

  Atsufumi Nakahashi, Tohru Taniguchi, Nobuaki Miura, Kenji Monde

  ORGANIC LETTERS 9 (23) 4741 - 4744 1523-7060 2007/11 [Refereed][Not invited]
   

  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.
• 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 0040-4039 2007/08 [Refereed][Not invited]
   

  (+)-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.
• Effects of central metal ions on vibrational circular dichroism spectra of Tris-(beta-diketonato)metal(III) complexes

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

  INORGANIC CHEMISTRY 46 (16) 6755 - 6766 0020-1669 2007/08 [Refereed][Not invited]
   

  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.
• Reassessing the structure of pyranonigrin

  Gerhard Schlingmann, Tohru Taniguchi, Haiyin He, Ramunas Bigelis, Hui Y. Yang, Frank E. Koehn, Guy T. Carter, Nina Berova

  JOURNAL OF NATURAL PRODUCTS 70 (7) 1180 - 1187 0163-3864 2007/07 [Refereed][Not invited]
   

  Fermentation extracts of the marine fungus Aspergillus niger LL-LV3020 were found to have relevant activity in a number of assays. Chemical screening of the extracts revealed that this organism produced numerous secondary metabolites in addition to its principal metabolite, citric acid. The compound with the most significant UV peak was isolated and its structure elucidated. Physical data suggested that this compound is identical with pyranonigrin A (1); however, our structure elucidation led to a different assignment than previously reported. On the basis of analysis of all data, we propose a correction to the structure of pyranonigrin A. Its absolute configuration was determined by electronic circular dichroism measurements in comparison with theoretical values calculated via ab initio time-dependent density functional theory and assigned as (7R)-3,7-dihydroxy-2-[(1E)-prop-1-enyl]-6,7-dihydropyrano[2,3-c]pyrrole-4,5-dione.
• Chiroptical analysis of glycoconjugates by vibrational circular dichroism (VCD)

  Taniguchi Tohru, Monde Kenji

  TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY 19 (107) 147 - 164 0915-7352 2007/05 [Refereed][Not invited]
   

  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.
• Absolute configuration determination using vibrational circular dichroism. Method for absolute configuration determination in the solution state without induction.

  Kenji Monde, Nobuaki Miura, Tohru Taniguchi

  Kagaku to Seibutsu 日本農芸化学会 45 (7) 455 - 458 0453-073X 2007 [Not refereed][Not invited]
  
• Spectrum-structure relationship in carbohydrate vibrational circular dichroism and its application to glycoconjugates

  Tohru Taniguchi, Kenji Monde

  CHEMISTRY-AN ASIAN JOURNAL 2 (10) 1258 - 1266 1861-4728 2007 [Refereed][Not invited]
   

  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.
• 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 1477-0520 2007 [Refereed][Not invited]
   

  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.
• 11 Vibrational Circular Dichroism (VCD) Application to Natural Products : Determination of Absolute Stereochemistry without Derivatization

  Taniguchi Tohru, Miura Nobuaki, Fukuzawa Masumi, Nakahashi Atsufumi, Monde Kenji

  Symposium on the Chemistry of Natural Products, symposium papers 天然有機化合物討論会 (48) 61 - 66 2006/09/15 

  Determination of absolute configuration has often required chemical derivatization. Vibrational circular dichroism (VCD), a recently developed chiroptical spectroscopy, measures differential absorption of left vs. right circularly polarized infrared light caused by molecular vibrational transition. VCD is becoming one of the most powerful and convenient technique for chiral studies, due to the applicability to all organic compounds without any derivatization in solution state with the aid of reliable theoretical calculation. We have applied this method to natural products. In this paper, we discuss VCD assignment of the absolute configurations, which are not easily determined by ordinary methods. Absolute stereochemistries of brominated marine sesquiterpenes from Laurencia 1, 2 and 4 were studied by VCD. Comprehensive conformation search followed by DFT calculation was performed to calculate VCD spectra. The observed VCD spectra showed good agreement with the calculated ones, by which compounds 1 and 2 were assigned as 7S,10S. Peroxidic diastereomers 4a and 4b were separated by chiral HPLC and their VCD spectra were measured. By comparison of experimental and theoretical VCD, their absolute stereochemistries were determined as 1R,4R,7S,10S and 1S,4S,7S,10S, respectively. This is the first case to apply VCD to determination of absolute configuration of the chiral peroxy compounds. Stereochemical studies of cruciferous phytoalexins 5-9 were also conducted by means of a nonempirical as well as an empirical manner. In this study, VCD was demonstrated to be effective also for tertiary alcohols and spiro-compounds. Stereochemistries on a glycerol moiety of lipids and glycolipids were also examined by VCD. By focusing on C=O stretching VCD, an empirical rule to distinguish the chirality of glycerol sn-2 carbon has been established.
• P-571 VIBRATIONAL CIRCULAR DICHROISM : A TECHNIQUE TO DETERMINE ABSOLUTE CONFIGURATION WITHOUT DERIVATIZATION AND CRYSTALLIZATION

  Taniguchi Tohru, Miura Nobuaki, Fukuzawa Masumi, Nakahashi Atsufumi, Monde Kenji

  International Symposium on the Chemistry of Natural Products 天然有機化合物討論会 2006 "P - 571" 2006/07/23
• 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 0040-4039 2006/06 [Refereed][Not invited]
   

  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.
• 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 0002-7863 2006/05 [Refereed][Not invited]
  
• 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 0899-0042 2006/05 [Refereed][Not invited]
   

  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.
• 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 0366-7022 2006/04 [Refereed][Not invited]
   

  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 alpha- and beta-D-glucopyranose conformations by the density functional theory

  N Miura, T Taniguchi, K Monde, SI Nishimura

  CHEMICAL PHYSICS LETTERS 419 (4-6) 326 - 332 0009-2614 2006/02 [Refereed][Not invited]
   

  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.
• 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 460 107 - 116 1542-1406 2006 [Refereed][Not invited]
   

  Vibrational circular dichroism (VCD) spectroscopy has been applied for monitoring in situ the photoinduced rewind of supramolecular helices in a liquid crystal. The monitored system was a room.-temperature liquid crystal, ZLI-1132, doped with a novel chiral Cr(III) complex. Under the illumination of UV light, (365nm), the photoracemization of the Cr(III) complex led to the rewind of helices in the chiral nematic phase. In, response to this, the VCD spectrum of the system exhibited the transient change, confirming the elongation of helical pitch length. The possibility of using the VCD spectrum as a memory of photoresponsive events is discussed.
• 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 0968-0896 2005/09 [Refereed][Not invited]
   

  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.
• A characteristic CH band in VCD of methyl glycosidic carbohydrates

  T Taniguchi, K Monde, N Miura, S Nishimura

  TETRAHEDRON LETTERS 45 (46) 8451 - 8453 0040-4039 2004/11 [Refereed][Not invited]
   

  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.
• Vibrational circular dichroism: Chiroptical analysis of biomolecules

  T Taniguchi, N Miura, SI Nishimura, K Monde

  MOLECULAR NUTRITION & FOOD RESEARCH 48 (4) 246 - 254 1613-4125 2004/09 [Refereed][Not invited]
  
• Specific band observed in VCD predicts the anomeric configuration of carbohydrates

  K Monde, T Taniguchi, N Miura, SI Nishimura

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 (31) 9496 - 9497 0002-7863 2004/08 [Refereed][Not invited]
   

  (Highlighted in Lett. Org. Chem. 2005, 2, 207.)
• 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 0040-4039 2003/08 [Refereed][Not invited]
   

  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.

Research Projects

• カルベノイド挿入反応を利用した含硫黄、窒素、酸素多環式化合物の合成法開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2020/04 -2023/03 

  Author : 浅川 倫宏, 谷口 透

   

  天然からも得られる2,3-置換インドリン骨格を有する化合物群は、その生物活性に興味が持たれており、新たな医薬品候補として期待されている。そのため、2,3-置換インドリン骨格の効率的な合成法の開発は、医薬品開発において重要である。しかしながら、現在知られている合成法は多段階を要することから、より短段階のものが求められている。そこで、本骨格の構築にC-H 挿入反応を利用すれば、より効率的に合成が可能である。近年、大きく進歩してきた不活性な C-H結合へのカルベン挿入反応は、炭素-炭素結合形成反応の際に求電子側に脱離基やカルボニル基を一切必要としない。そのため、前駆体となる水酸基等からの変換の必要もなく、煩雑な保護や脱保護の段階も軽減する魅力的かつ力量のある合成方法論である。また、不活性な C-H 結合への直接的な官能基化は、高いアトムエコノミーや合成の短段階化による効率化へと繋がる。しかし、本法によるヘテロ環合成法の開発は、主として含酸素芳香環への適用報告のみであった。そこで私は、未だ報告例の無かったアニリン窒素隣接位への C-H挿入反応よるインドリン構築法の開発を検討した。 本反応の検討を行うため、反応基質の合成に着手した。従来予定していた金属触媒によるカップリング反応での基質合成は困難であった。そのため、より簡便に合成できる方法を計画した。そして目的のジアゾ化合物を合成し、初期検討としてロジウム(II)触媒を用いたC-H挿入反応を試したところ、目的の反応は進行し、インドリン骨格を有する化合物が得られることを見出した。また、基質の適用性の範囲を調べるため、類縁体の合成に着手し、さらなる検討の準備を進めた。一方で、絶対立体配置の解析のため、構造からのスペクトル予測を進めた。
• Development of novel stereochemical analytical technique of biomolecules by the VCD exciton chirality method

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2019/04 -2023/03 

  Author : 門出 健次, 谷口 透, 村井 勇太

   

  昨年に引き続き、アルキン、アジド、ニトリル等のIR官能基のVCD励起子キラリティー法への応用可能性を検証するために、各種IR官能基を有する化合物を合成し、その実測VCDを検証した。生体関連中分子に対して、VCD励起子キラリティー法を適用させるため、中分子として、アシルセラミドを選び、分子内の二つのカルボニル基に対してのVCD励起子キラリティー法の適用を考えた。アシルセラミドは、人間の皮膚のバリア機能を担う巨大スフィンゴ脂質分子である。近年、アトピー性皮膚炎の原因がアシルセラミド合成酵素の欠損によるものであることが発見されている。創薬的見地からも、この巨大アシルセラミド分子の全合成研究を実施する。本分子には二つの不斉炭素があるが、その絶対配置決定（例えば天然体）は、通常の方法では極めて困難である。まず、超長鎖脂肪酸を有するセラミドの二級水酸基にアシル基を導入することにより、VCD励起子キラリティー法の適用が可能となると考えた。アシルセラミドは、細長い分子であるが、皮膚上で特殊な構造をとると考えられている。化学合成による純粋なサンプル供給を目指し、スフィンゴ塩基部分、および、長鎖部位の合成に成功し、全合成にむけての部分合成を実施した。特に、長鎖脂肪酸の合成に注力した。オメガ９位に二重結合を有する超長鎖脂肪酸は、これまでにほとんど合成例がない。超長鎖炭化水素の反応性の特性を溶媒により制御する方法を見出し、Wittig反応を基本としたカップリング反応により、C34:1の脂肪酸の合成に成功した。
• Development of structural analysis methods for middle-sized and polar molecules by VCD spectroscopy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2018/04 -2022/03 

  Author : Taniguchi Tohru

   

  Middle-sized natural products (M.W. 500 to 2000) such as oligosaccharides, cyclic peptides, macrolides, and other metabolites are promising drug candidates beyond Lipinski’s rule of 5. Because middle-sized molecules target, for example, protein-protein interactions more efficiently than small molecules do, a large number of such drugs have been approved and under development in recent years. For the exploration of such natural products and their synthetic derivatives, their structural elucidation is one of the major bottlenecks as they possess multiple chiral centers. In this work, we developed new methods for structural analysis of middle-sized molecules by using vibrational circular dichroism (VCD) spectroscopy. Furthermore, this work achieved the first preparation of carbodiimides with one-handed axial chirality.
• 赤外円二色性とラマン光学活性による中分子・極性分子の高精度構造解析法の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2019 -2022 

  Author : 谷口 透

   

  中分子や柔軟分子のような新奇分子の構造を簡便に分析する手法の開発に向けて、基課題（18H02093）では赤外円二色性（VCD）分光法を用いた研究を進めているが、本課題(18KK0394)ではVCDに加えてラマン光学活性（ROA）分光法を用いた研究を進めている。本申請研究では、ROA測定用の各種分子を国内で有機合成し、国際共同研究先にてROAスペクトルを測定、さらに得られたROAスペクトルを国内における理論計算によって解釈することによる構造解析法の確立を目指したVCD・ROA研究を推進する計画だった。しかし、2020年度に引き続き2021年度もコロナウイルスの影響によって入国制限・帰国制限・海外出張制限を課されるとともに、共同研究先のロイヤルメルボルン工科大学の研究室も長期にわたって閉鎖されたため、渡航できなかった。 本研究に関連した国内での研究は次の通りである。ROAスペクトル（2019年に測定）を元に構造を分析する方法として、分子動力学（MD）計算とQM/MM法を併用したスペクトル構造計算法の確立を国内で進めてきた。本法はまだ改良の余地があるものの、水中における単糖のスペクトルを計算するには十分な精度が得られるようになってきた。この計算法を利用し、水中における単糖の構造についてVCDスペクトルを用いて解明し、論文発表した。また2400-1900 cm-1領域の振動プローブについても研究を進め、振動領域光学活性測定に有用な官能基について知見を得て、本結果についても論文発表した。
• Development of Non-Enzymatic Method to Translate D-Nucleic Acid to L-Nucleic Acid

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2016/04 -2018/03 

  Author : Taniguchi Tohru

   

  Aiming both at creation of mirror-image life and at development of nucleic acid drugs resistant to nucleases, this work studied toward creation of non-enzymatic reaction to translate D-nucleic acid to L-nucleic acid. During the synthesis of L-nucleotide monomers, we succeeded in developing an efficient glycosidation reaction to connect a sugar and a nucleobase. We also established a new method to elucidate the configuration and conformation of furanoside and nucleoside by using vibrational circular dichroism. L-Nucleotides obtained in this study were submitted to solid-state synthesis, which yielded several oligonucleotides containing L-nucleotides. Oligonucleotides containing L-methylcytidines showed high stability when forming a duplex with D-oligonucleotides.
• 3D structural analysis of (macro)molecules using VCD in the region above 1900 cm-1

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2014/04 -2017/03 

  Author : Taniguchi Tohru

   

  Development of a method to analyze molecular stereostructures provides a detailed understanding of the functions of various molecules such as medicines and enzymes and of the origin of life. This work has established a new convenient method for analyzing molecular stereostructures by using vibrational circular dichroism (VCD) spectroscopy. For example, this work has demonstrated its effectiveness toward the secondary structure of macromolecules such as polyesters. Another example for the use of our VCD method is facile determination of lipid molecules that are suggested to have involved in the development of life. Because VCD spectroscopy provides structural information that can not be obtained by the other available methods, this method should deepen our understandings on molecular stereostructures.
• Development of the novel determination methodology for absolute configuration without theoretical calculation

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2012/04 -2015/03 

  Author : MONDE Kenji, TANIGUCHI Tohru, MURAI Yuta

   

  Vibrational circular dichroism (VCD) is a reliable and non-empirical method which can determine absolute configuration. However, ab initio theoretical calculation for its conformational analysis of a target molecule is essential. In this project, a new methodology for determination of absolute configuration without its theoretical calculation has been developed by utilizing a huge bisignate VCD signal caused by their interaction of two IR functional groups such as carbonyl groups in a target molecule. This novel methodology named as “VCD exciton chirality method” has been applied to a variety of carbohydrates, steroids, complex natural products, acyclic biological active lipids, and poly lactic acid as a polymer, which shows its high applicability.
• Studies on the Relationship between the Triple Helical Structure and Immunostimulatory Activity of beta-glucan

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2011 -2013 

  Author : TANIGUCHI Tohru

   

  The secondary and higher-order structure of oligo- and polysaccharides has been suggested to be important in exhibiting their biological activity; however, few methods have been available to study their relationship. In this study, through basic studies on vibrational circular dichroism (VCD), we developed a "VCD exciton chirality method", which allowed us to study stereostructures of complex molecules. By using this method, we successfully detected the conformational changes of beta glucan triple helix. Aiming at identifying the minimum structure of beta glucan to form triple helix, we also developed a new method to synthesize short beta glucan.
• βー1,3ーグルカンの高次構造に着目したVCD・合成・免疫学研究

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2010 -2011 

  Author : 谷口 透

   

  海藻やキノコに含まれるβ-1,3-グルカンは免疫賦活剤や抗がん剤として臨床に用いられているものの、その特異な三重らせん高次構造のために詳細な分子作用機序は不明である。本研究では、(1)VCD(赤外領域円二色性)を用いた糖鎖高次構造解析法の確立、(2)β-1,3-グルカンフラグメントの有機合成および各フラグメントの三重らせん形成能の検討、(3)得られた三重らせんフラグメントの高次構造と免疫活性化能の相関検討、を行う。本研究の達成により今後、NMRや共結晶を用いたβ-1,3-グルカンとその標的タンパク質との詳細な相互作用の解析を行うことも可能となり、より生理活性の高いβ-1,3-グルカン誘導体の開発、ならびに新規デリバリー法開発に資すると期待される。 β-1,3-グルカン研究における問題点として、多糖の高次構造を解析する有効な手法が確立されていないことが挙げられる。そこで本研究ではまず、VCDによる多糖の高次構造解析法の開発に着手した。カードラン、シゾフィランなどのβ-1,3-グルカンのVCDを各種条件下で測定したところ、VCDが多糖の高次構造解析に有効であるという予備的知見を得た。これは、VCDを多糖の高次構造解析に用いた初の研究例であり、本手法が多糖全般の高次構造理解の深化に資すると期待される。 また、β-1,3-グルカンフラグメントの効率的新規合成法の開発に着手した。本研究では、G1cβ1→3G1cβ1→[G1cβ1→3]G1cのような分岐度0.33の4糖ユニットをまず合成し、これをベースに8糖、16糖、24糖などの合成を検討している。平成22年度では、基本となる4糖ユニットの合成に着手し、各種反応条件を最適化してきた。今後、これらのユニットを結合させる各種グリコシデーション法を検討し、合成を達成し、VCD研究ならびに免疫賦活活性試験に供したいと考えている。
• 生物によるキラル円偏光識別とその分子機構の解明

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2008 -2010 

  Author : 門出 健次, 谷口 透

   

  本研究では、「生物がキラルな円偏光を識別するか?」という単純な命題を明らかにすることを目的としている。昨年度は緑藻クラミドモナスに着目し、企業と共同開発した円偏光装置を用いて「増殖」の様子を観察したが、左右の円偏光で顕著な差は観察されなかった。従って本年度は、クラミドモナスの「走光性」及び「光合成活性」に着目し実験を行った。 1)円偏光照射対象生物であるクラミドモナスは弱光に対しては近づき(正の走光性)、強光からは逃げる(負の走光性)性質をもつ。本現象にはキラルな光受容体「ロドプシン」が関与しており、左右の円偏光で発色団の光異性化効率に差異が出る可能性がある。本性質に対する円偏光の効果を調査するため、本年度は植物生物学者と共に新たな実験系の確立を行った。実際ODの変化により走光性を観察したところ、左右で走光性に顕著な違いは見られなかった。これはロドプシンにおいて左右円偏光吸収強度の差が極めて小さいためと考えられる。 2)前年度に左右円偏光でクラミドモナスの増殖に違いが出ないことを確認したが、光合成と増殖は必ずしもリニアな関係に無いことから、本年度はクラミドモナスの光合成に対する円偏光の効果を調査した。本学低温科学研究所の研究者の協力のもと、円偏光照射時の光合成活性を測定し、円偏光の方向性が光合成に与える影響を調査した。結果、光合成活性には差が出ないことがわかった。 3)円偏光照射対象生物を拡大し、シアノバクテリアについても同様の実験が可能か検討した。本バクテリアはクラミドモナスとは別の光受容体を有することから、異なる応答が期待されたが、クラミドモナスと同様顕著な差は観測されなかった。本年度は左右円偏光を識別する生物、生命現象の発見には至らなかったが、上記実験は世界で初めての試みであり、今後の大きな知見になると考えている。
• Construction of the standard chiroptical analysis method by vibrational circular dichroism

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2008 -2010 

  Author : MONDE Kenji, MIURA Nobuaki, TANIGUCHI Tohru, MIURA Nobuaki

   

  Glycerolipids are essential substances for sustaining our life. Although the number of their chiral carbon is only one like most of amino acids, their stereochemistry has not been assigned with ease. In order to establish a new analytical method for determination of their absolute configurations, optically pure glycerolipids and related compounds were prepared by chemical synthesis, and subjected to the "Vibrational Circular Dichromism" measurement. The precise analysis of their spectral data resulted in a discovery of an empirical rule on the stereochemistry of diacylglycerolipids including glycolipids for the first time.