研究者データベース
| 鈴木 孝洋(スズキ タカヒロ) |
| 理学研究院 化学部門 有機・生命化学分野 |
| 准教授 |
Last Updated :2024/05/09
研究活動情報
論文
- Takahiro SuzukiJournal of Synthetic Organic Chemistry, Japan 2024年04月01日
- Mari Shimura, Nobuyo Higashi-Kuwata, Asuka Fujiwara, Mai Taniguchi, Takayuki Ichinose, Fumie Hamano, Masaaki Uematsu, Takato Inoue, Satoshi Matsuyama, Takahiro Suzuki, Arun K. Ghosh, Hideo Shindou, Takao Shimuzu, Hiroaki MitsuyaAntiviral Research 2024年03月
- Kazuto Sato, Tomoyuki Fujita, Takashi Takeuchi, Takahiro Suzuki, Kazutada Ikeuchi, Keiji TaninoOrganic & Biomolecular Chemistry 2024年
- Tohru Taniguchi, Mutmainah, Shu Takimoto, Takahiro Suzuki, Soichiro Watanabe, Fuyuhiko Matsuda, Taiki Umezawa, Kenji MondeOrganic & biomolecular chemistry 21 3 569 - 574 2023年01月18日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 CCC 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 CCC 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.
- Kazutada Ikeuchi, Shota Haraguchi, Ryo Fujii, Hidetoshi Yamada, Takahiro Suzuki, Keiji Tanino2022年12月28日This paper describes the total synthesis of (+)-coriamyrtin, a picrotoxane-type sesquiterpene. The natural product is widely known as a neurotoxin of the Coriariaceae family and bears a highly functionalized cis-hydrindane skeleton. Despite being biologically and synthetically attractive molecule, only two examples of the total synthesis are reported to date. Our synthetic strategy involves the highly stereoselective construction of the cis-hydrindane skeleton via the desymmetric strategy of a 1,3-cyclopentanedione moiety using an intramolecular aldol reaction and elaborate functionalization of the cyclopentane ring in the bicyclic structure for the formation of the 1,3-diepoxide moiety of coriamyrtin. Our method could be applied to synthesize various natural products with similar bicyclic skeletons and to expand neurobiological studies using synthesized products.
- Kazutada Ikeuchi, Yusuke Ozoe, Ranmaru Kato, Takahiro Suzuki, Keiji TaninoSynthesis 2022年12月27日2,2-Disubstituted-1,3-cyclopentanediones are versatile building blocks for synthesizing complex natural products with bicyclic structures including cyclopentane rings. The reported method for the synthesis of these compounds involves the semi-pinacol rearrangement of a Mukaiyama-aldol adduct prepared from a ketone/ketal and 1,2-bis(trimethylsilyloxy)cyclobutene. However, the adoption of α-oxy-functionalized ketones/ketals is quite difficult, as demonstrated by our experiments. To overcome this limitation of the method, we used 2-acylfuran derivatives as the reactants to synthesize 2,2-disubstituted-1,3-cyclopentanediones. Furthermore, two reaction conditions, that is, the use of 1.4 equivalents of a boron trifluoride-diethyl ether complex or 0.4 and 0.2 equivalents of trimethylsilyl triflate and methoxytrimethylsilane, respectively, were established for the conversion of 2-acylfurans into the corresponding 1,3-cyclopentanediones in acceptable yields. The transformations of the furan rings in the obtained products were also investigated.
- Takahiro Suzuki, Wataru Ikeda, Ayaka Kanno, Kazutada Ikeuchi, Keiji TaninoChemistry – A European Journal 2022年12月18日
- Ranmaru Kato, Hiroki Saito, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoOrganic Letters 2022年11月04日
- Takahiro SuzukiOrganics 2022年09月09日
- Kosuke Kato, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoOrganic Letters 24 35 6407 - 6411 2022年09月09日 [査読有り][通常論文]
- Takahiro SuzukiOrganics 2022年09月
- Two-Step Method for Constructing a Quaternary Carbon Atom with a Geminal Divinyl Group from a KetoneRyota Ogura, Kazuto Satoh, Wataru Kiuchi, Kosuke Kato, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoOrganic Letters 24 28 5040 - 5044 2022年07月22日
- Hiroki Saito, Ranmaru Kato, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoOrganic Letters 2021年12月17日 [査読有り]
- Yuki Yukutake, Takahiro Hiramatsu, Ryusei Itoh, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoSynlett 33 03 296 - 300 2021年11月16日Synthetic studies on an ABC-ring model of Tubiferal A, a triterpenoid isolated from the fruit bodies of the Tubifera dimorphotheca myxomycete, are described. The stereogenic centers at the angular positions were constructed through the stereoselective addition of a C-ring allylborane followed by an Eschenmoser–Claisen rearrangement reaction prior to the formation of the AB-ring system by a double intramolecular alkylation reaction of a dichloro nitrile intermediate.
- Kazutada Ikeuchi, Tomonari Sasage, Gen Yamada, Takahiro Suzuki, Keiji TaninoOrganic Letters 23 23 9123 - 9127 2021年11月11日
- Takahiro Suzuki, Soichiro Watanabe, Wataru Ikeda, Susumu Kobayashi, Keiji TaninoThe Journal of Organic Chemistry 86 21 15597 - 15605 2021年11月05日
- Jun-ichiro Kishi, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoSynlett 33 02 196 - 200 2021年10月29日
- Ranmaru Kato, Hiroki Saito, Shoko Uda, Daisuke Domon, Kazutada Ikeuchi, Takahiro Suzuki, Keiji TaninoOrganic Letters 23 22 8878 - 8882 2021年10月29日
- Takahiro Suzuki, Riko Nagahama, Muhammad Aiman Fariz, Yuki Yukutake, Kazutada Ikeuchi, Keiji TaninoOrganics 2 3 306 - 312 2021年09月02日Illisimonin A is a new sesquiterpene isolated from Illicium simonsii, and it possesses a novel 5/5/5/5/5 pentacyclic skeleton. The tricyclic skeleton of illisimonin A, tricyclo[5.2.1.01,5]decane, is presumed to be biosynthesized from allo-cedranes via a skeletal rearrangement. Herein, we report the concise synthesis of highly oxidized allo-cedranes by an intramolecular Diels–Alder reaction using ortho-benzoquinones and demonstrate the biomimetic transformation of allo-cedranes by a retro-Claisen/aldol pathway.
- Takahiro Suzuki, Takeshi Koyama, Kenta Nakanishi, Susumu Kobayashi, Keiji TaninoThe Journal of Organic Chemistry 85 15 10125 - 10135 2020年08月07日
- Takahiro Suzuki, Takamune Yanagisawa, Keiji TaninoHETEROCYCLES 99 2 848 - 848 2019年 [査読有り][招待有り]
- Takahiro Suzuki, Soichiro Watanabe, Muhammet Uyanik, Kazuaki Ishihara, Susumu Kobayashi, Keiji TaninoOrganic Letters 20 13 3919 - 3922 American Chemical Society ({ACS}) 2018年07月06日 [査読有り][通常論文]
- 鈴木孝洋有機合成化学協会誌 76 5 462 - 465 2018年 [査読有り][招待有り]
(+)-Iso-A82775C is one of the proposed biosynthetic precursors of chloropupukeananin and an important intermediate for related bioactive natural products. The first enantioselective total synthesis of (+)-iso-A82775C toward the eventual biomimetic total synthesis of chloropupukeananin has been achieved. The key steps of the total synthesis are the enantioselective Diels-Alder reaction of 4-bromo-3-hydroxy-2-pyrone with methyl 2-chloroacrylate catalyzed by cinchona alkaloids and the <i>anti</i>-selective Cu-mediated S<sub>N</sub>2' reaction to afford the axially chiral vinylallene moiety. Herein the details and inside stories are disclosed.</p> - Takahiro Suzuki, Masataka Fujimura, Kazuhiro Fujita, Susumu KobayashiTETRAHEDRON 73 26 3652 - 3659 2017年06月 [査読有り][招待有り]
A highly convergent total synthesis of (+)-methynolide, based on two types of stereoselective aldol reaction, was achieved. The C1-C8 and C9-C11 fragments of (+)-methynolide were prepared by a vinylogous Mukaiyama aldol reaction using a vinyl ketene silyl N,O-acetal, and a Ti-mediated aldol reaction of a lactyl-bearing chiral oxazolidin-2-one, respectively. Yamaguchi esterification of both fragments and ring-closing metathesis afforded (+)-methynolide. (C) 2017 Elsevier Ltd. All rights reserved. - Takahiro Suzuki, Soichiro Watanabe, Susumu Kobayashi, Keiji TaninoORGANIC LETTERS 19 4 922 - 925 2017年02月 [査読有り][通常論文]
(+)-Iso-A82775C is a proposed biosynthetic precursor of the chloropupukeananin family and an important intermediate for related natural products. The first enantioselective total synthesis of (+)-iso-A82775C (18 steps, 2.2% overall yield) toward the eventual biomimetic total synthesis of chloropupukeananin is described. The key steps are (1) the enantioselective Diels Alder reaction of 4-bromo-3-hydroxy-2-pyrone with methyl 2-chloroacrylate using cinchonine as an organocatalyst and (2) the anti-selective Cu-mediated S(N)2' reaction to afford the axially chiral vinylallene moiety. - Shu Nishikori, Kenji Takemoto, Shinji Kamisuki, Syo Nakajima, Kouji Kuramochi, Senko Tsukuda, Masashi Iwamoto, Yuri Katayama, Takahiro Suzuki, Susumu Kobayashi, Koichi Watashi, Fumio SugawaraJOURNAL OF NATURAL PRODUCTS 79 2 442 - 446 2016年02月 [査読有り][通常論文]
New diazabicyclo[2.2.2]octane derivatives, peniciherquamides A-C (1-3), and a novel herqueinone derivative, neoherqueinone (5), were isolated from a fungal culture broth of Penicillium herquei. The structures of these novel compounds were determined by interpretation of spectroscopic data (1D/2D NMR, MS, and IR). Four known compounds, preparaherquamide (4), peniciherqueinone (6), and herqueinone/isoherqueinone (7/7a), were also obtained. The isolated compounds were tested for anti hepatitis C virus (HCV) activity, and peniciherquamide C (3) was found to display an IC50 value of 5.1 mu M. To our knowledge, this is the first report of a diazabicyclo[2.2.2]octane derivative with anti-CV activity. - Kenji Usui, Takahiro Suzuki, Masahisa NakadaTETRAHEDRON LETTERS 56 10 1247 - 1251 2015年03月 [査読有り][通常論文]
A highly stereoselective intramolecular Diels Alder (IMDA) reaction for the construction of the AB ring moiety of bruceantin is described. The product of the IMDA reaction comprises a trans-AB ring junction and stereotetrad including an all carbon quaternary stereogenic center, wherein three stereogenic centers correspond to those of bruceantin. Functional groups embedded in the product are suitable for a variety of transformations. Hence, this IMDA product could be a useful intermediate for the enantioselective total synthesis of not only bruceantin, but also other bioactive compounds. (C) 2015 Elsevier Ltd. All rights reserved. - Noriyuki Takahashi, Keiji Tamura, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiTETRAHEDRON LETTERS 56 2 327 - 330 2015年01月 [査読有り][通常論文]
The spiroiridal triterpenoids show interesting biological activities, such as a piscicidal activity, PKC activation, and molluscicidal activity. Herein, the first synthesis of the functionalized spiro[4.5]decane skeleton of spiroiridal triterpenoids was accomplished. The characteristic features of the present synthesis are the Claisen rearrangement of 2-(alkenyl)dihydropyran developed by our group and the efficient transformation into the key intermediate (+)-6. (C) 2014 Elsevier Ltd. All rights reserved. - Kaori Takakusagi, Yoichi Takakusagi, Takahiro Suzuki, Aya Toizaki, Aiko Suzuki, Yaichi Kawakatsu, Madoka Watanabe, Yukihiro Saito, Ryushi Fukuda, Atsuo Nakazaki, Susumu Kobayashi, Kengo Sakaguchi, Fumio SugawaraEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 90 809 - 821 2015年01月 [査読有り][通常論文]
Roxithromycin (RXM) is a semi-synthetic fourteen-membered macrolide antibiotic that shows anti-angiogenic activity in solid tumors. In the present study, we conducted biopanning of T7 phage-displayed peptides either on a 96-well formatted microplate, a flow injection-type quartz-crystal microbalance (QCM) biosensor, or a cuvette-type QCM. RXM-selected peptides of different sequence, length and number were obtained from each mode of screening. Subsequent bioinformatics analysis of the RXM-selected peptides consistently gave positive scores for the extracellular domain (E458-T596) of angiomotin (Amot), indicating that this may comprise a binding region for RXM. Bead pull down assay and QCM analysis confirmed that RXM directly interacts with Amot via the screen-guided region, which also corresponds to the binding site for the endogenous anti-angiogenic inhibitor angiostatin (Anst). Thus, multimodal biopanning of T7PD revealed that RXM binds to the extracellular domain on Amot as a common binding site with Anst, leading to inhibition of angiogenesis-dependent tumor growth and metastasis. These data might explain the molecular basis underlying the mechanism of action for the anti-angiogenic activity of RXM. (C) 2014 Elsevier Masson SAS. All rights reserved. - Takahiro Suzuki, Hiroshi Okuyama, Atsuhiro Takano, Shinya Suzuki, Isao Shimizu, Susumu KobayashiJOURNAL OF ORGANIC CHEMISTRY 79 6 2803 - 2808 2014年03月 [査読有り][通常論文]
The synthesis of a novel hydrocarbon, dibarrelane, has been accomplished in 11 steps via an intramolecular REDDA reaction of a masked o-benzoquinone, followed by Clemmensen reduction and Barton decarboxylation. The twisted structure of the tetracyclic dibarrelane skeleton was also clarified via X-ray crystallography. Finally, it was proposed that dibarrelane has C-2 symmetry rather than C-2v symmetry. - Satomi Shimura, Masahiro Ishima, Syo Nakajima, Toshitaka Fujii, Natsumi Himeno, Kentaro Ikeda, Jesus Izaguirre-Carbonell, Hiroshi Murata, Toshifumi Takeuchi, Shinji Kamisuki, Takahiro Suzuki, Kouji Kuramochi, Koichi Watashi, Susumu Kobayashi, Fumio SugawaraJournal of the American Chemical Society 135 50 18949 - 18956 2013年12月18日 [査読有り][通常論文]
The first total synthesis of MA026 and the identification of its candidate target protein for anti-hepatitis C virus activity are presented. MA026, a novel lipocyclodepsipeptide isolated from the fermentation broth of Pseudomonas sp. RtIB026, consists of a cyclodepsipeptide, a chain peptide, and an N-terminal (R)-3-hydroxydecanoic acid. The first subunit, side chain 2, was prepared by coupling fatty acid moiety 4 with tripeptide 5. The key macrocyclization of the decadepsipeptide at l-Leu10-d-Gln11 provided the second subunit, cyclodepsipeptide 3. Late-stage condensation of the two key subunits and final deprotection afforded MA026. This convergent, flexible, solution-phase synthesis will be invaluable in generating MA026 derivatives for future structure-activity relationship studies. An infectious hepatitis C virus (HCV) cell culture assay revealed that MA026 suppresses HCV infection into host hepatocytes by inhibiting the entry process in a dose-dependent manner. Phage display screening followed by surface plasmon resonance (SPR) binding analyses identified claudin-1, an HCV entry receptor, as a candidate target protein of MA026. © 2013 American Chemical Society. - Atsuo Nakazaki, Kanako Iwakiri, Tomohiro Hirano, Takahiro Suzuki, Susumu KobayashiCHEMICAL & PHARMACEUTICAL BULLETIN 61 5 587 - 591 2013年05月 [査読有り][通常論文]
Deprotection of a methoxymethyl (MOM) group on an oxindole nitrogen under basic conditions is demonstrated. The mechanisms of both the deprotection and the formation of N-methyloxindole were revealed by using deuterated NaOMe-MeOH in mechanistic studies. - Takahiro Suzuki, Yuria Miyajima, Kaname Suzuki, Kanako Iwakiri, Masaki Koshimizu, Go Hirai, Mikiko Sodeoka, Susumu KobayashiORGANIC LETTERS 15 7 1748 - 1751 2013年04月 [査読有り][通常論文]
The biomimetic synthesis of the advanced model compound of chloropupukeananin has been achieved. The present synthesis features an unexpected enantiomer-differentiating Diels-Alder/carbonyl-ene cascade under high-pressure conditions and a base-promoted migration of the salicyl group. - 鈴木 孝洋有機合成化学協会誌 70 10 1069 - 1070 社団法人 有機合成化学協会 2012年10月01日 [査読有り][招待有り]
Kinamycins and lomaiviticins are potent antiproliferative antimicrobial natural products possessing a unique diazotetrahydrobenzo[b]fluorene moiety. Biological and structural features of these compounds have attracted much attention from synthetic chemists. In this review, recent synthetic efforts toward lomaiviticins reported by Shair's group and Herzon's group are described. - Ryo Tanaka, Kentaro Ohishi, Noriyuki Takanashi, Tomohiko Nagano, Hiroshi Suizu, Takahiro Suzuki, Susumu KobayashiORGANIC LETTERS 14 18 4886 - 4889 2012年09月 [査読有り][通常論文]
The first synthesis of decahydrofluorene core 4 of pyrrocidines was accomplished. The cis,trans-fused tricyclic ring system was stereoselectively constructed via Diels-Alder reaction using two Danishefsky dienes. - Emi Nozaki, Mari Gotoh, Ryo Tanaka, Masaru Kato, Takahiro Suzuki, Atsuo Nakazaki, Harumi Hotta, Susumu Kobayashi, Kimiko Murakami-MurofushiBIOORGANIC & MEDICINAL CHEMISTRY 20 10 3196 - 3201 2012年05月 [査読有り][通常論文]
Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator possessing cyclic phosphate ring, which is necessary for its specific biological activities. To stabilize cyclic phosphate ring of cPA, we synthesized a series of cPA derivatives. We have shown that racemic 3-S-cPA, with a phosphate oxygen atom replaced with a sulfur atom at the sn-3, was a more effective autotaxin (ATX) inhibitor than cPA. In this study, we showed that racemic 3-S-cPA also had potent biological activities such as inhibition of cancer cell migration, suppression of the nociceptive reflex, and attenuation of ischemia-induced delayed neuronal cell death in the hippocampal CA1. Moreover, we synthesized both enantiomers of palmitoleoyl derivative of 3-S-cPA, and found that the chirality of 3-S-cPA is not involved in ATX inhibition. Based on these findings, racemic 3-S-cPA is suggested as an effective therapeutic compound like cPA. (C) 2012 Elsevier Ltd. All rights reserved. - Hayato Hosoi, Nobuyuki Kawai, Hideki Hagiwara, Takahiro Suzuki, Atsuo Nakazaki, Ken-ichi Takao, Kazuo Umezawa, Susumu KobayashiCHEMICAL & PHARMACEUTICAL BULLETIN 60 1 137 - 143 2012年01月 [査読有り][通常論文]
We describe the total synthesis and structural determination of (+)-akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include the resolution of beta,gamma-unsaturated ketone (+/-)-2a with chiral sulfoximine 6. The absolute stereochemistry was determined by comparison of the specific optical rotation data of (+)-1 and (-)-1 with that of natural akaterpin. - Kazuhiro Fujita, Ryosuke Matsui, Takahiro Suzuki, Susumu KobayashiANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 29 7271 - 7274 2012年 [査読有り][通常論文]
- Hayato Hosoi, Nobuyuki Kawai, Hideki Hagiwara, Takahiro Suzuki, Atsuo Nakazaki, Ken-ichi Takao, Kazuo Umezawa, Susumu KobayashiTETRAHEDRON LETTERS 52 38 4961 - 4964 2011年09月 [査読有り][通常論文]
We describe the first total synthesis and structural determination of akaterpin, an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include a regio- and stereoselective C-alkylation at the angular C1' position and an exo-selective intermolecular Diels-Alder reaction. The relative stereochemistry was determined by a comparison of the NMR spectra of synthetic akaterpin with those of natural akaterpin. (C) 2011 Elsevier Ltd. All rights reserved. - Ryo Tanaka, Masaru Kato, Takahiro Suzuki, Atsuo Nakazaki, Emi Nozaki, Mari Gotoh, Kimiko Murakami-Murofushi, Susumu KobayashiBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 21 14 4180 - 4182 2011年07月 [査読有り][通常論文]
The efficient synthesis of 3-O-thia-cPAs (4a-d), sulfur analogues of cyclic phosphatidic acid (cPA), has been achieved. The key step of the synthesis is an intramolecular Arbuzov reaction to construct the cyclic thiophosphate moiety. The present synthetic route enables the synthesis of 4a-d in only four steps from the commercially available glycidol. Preliminary biological experiments showed that 4a-d exhibited a similar inhibitory effect on autotaxin (ATX) as original cPA. (C) 2011 Elsevier Ltd. All rights reserved. - Different Modes of Cyclization in Zoanthamine Alkaloid System, Bisaminal versus Spiroketal FormationTakahiro Nakajima, Daisuke Yamashita, Kaname Suzuki, Atsuo Nakazaki, Takahiro Suzuki, Susumu KobayashiORGANIC LETTERS 13 12 2980 - 2983 2011年06月 [査読有り][通常論文]
Bisaminal cyclization in the zoanthamine alkaloid system was strongly affected by the stereochemistry of the C4 methyl. While cyclization of the (4S)-methyl precursor gave only a bisaminal compound, cyclization of the (4R)-methyl isomer produced both spiroketal and bisaminal products. - 鈴木(田中) 奈津美, 鈴木 孝洋, 松村 岳彦, 細谷 洋介, 中里 知幸, 中田 雅久Journal of Synthetic Organic Chemistry Japan 69 6 646 - 660 2011年06月 [査読有り][通常論文]
An enantioselective total synthesis of (−)-FR182877 is described. This total synthesis features 1) the one-pot stereoselective tandem IMDA-IMHDA reaction which affords the tetracyclic compound including the ABCD ring system of (−)-FR182877 with the correct new seven stereogenic centers, 2) the palladium-mediated 7-exo-trig intramolecular Heck reaction for the construction of the highly strained seven-membered F-ring, and 3) the iridium-mediated isomerization of the allylic alcohol to the α-methyl ketone followed by epimerization and the stereoselective reduction to furnish all the stereogen... - Yoichi Iwasaki, Ryosuke Matsui, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiCHEMICAL & PHARMACEUTICAL BULLETIN 59 4 522 - 524 2011年04月 [査読有り][通常論文]
We have developed a high-yielding and stereoselective vinylogous Mukaiyama aldol reaction (VMAR) of alpha-haloenals. Contrary to the simple alpha,beta-unsaturated aldehyde, alpha-haloenals were found to be reactive affording the corresponding VMAR adducts in excellent yields. Some transformations of VMAR adducts by Pd-mediated cross-coupling were also examined in order to demonstrate the synthetic utility of VMAR of alpha-haloenals. - Yuna Sato, Kouji Kuramochi, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiTETRAHEDRON LETTERS 52 5 626 - 629 2011年02月 [査読有り][通常論文]
The second generation synthesis of (+)-pseudodeflectusin (1), a potential antitumor agent, has been achieved. The key synthetic step is the cascade reaction involving Diels-Alder reaction, lactonization, and decarboxylation to give cycloadduct 6 with complete regioselectivity in good yield. We found that NaH is the best base to facilitate the Diels-Alder reaction of hydroxypyrone 7 with alkyne 8. The present synthetic route enables the total synthesis of (+)-1 in only five-steps from the known compounds 7 and 8. (C) 2010 Elsevier Ltd. All rights reserved. - Weiwei Tian, Lohitha Rao Chennamaneni, Takahiro Suzuki, David Y-K ChenEUROPEAN JOURNAL OF ORGANIC CHEMISTRY 6 1027 - 1031 2011年02月 [査読有り][通常論文]
In this article, a Lewis acid mediated 1,4-addition/formal [3+2] cycloaddition reaction engaging functionalized beta-carboline and 1,4-benzoquinone has been demonstrated. Application of this developed technology facilitated the construction of the challenging C-9'-C-15 quaternary center linkage in the dimeric indole alkaloid, haplophytine, and enabled the preparation of an advanced key intermediate en route to the total synthesis of this historical natural product. - Yuta Onodera, Takahiro Suzuki, Susumu KobayashiORGANIC LETTERS 13 1 50 - 53 2011年01月 [査読有り][通常論文]
An efficient total synthesis of (+)-nafuredin-gamma has been achieved in 10 steps from (E)-3-(tributylstannyl)propenal. The synthesis features direct construction of an anti-1,2-diol moiety via a Ti-mediated aldol reaction of lactyl derivative and rapid fragment assembly, which relied on well-established Pd chemistry. - Takahiro Suzuki, Aya Sasaki, Naoki Egashira, Susumu KobayashiANGEWANDTE CHEMIE-INTERNATIONAL EDITION 50 39 9177 - 9179 2011年 [査読有り][通常論文]
- Ryosuke Matsui, Kentaro Seto, Yttna Sato, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiANGEWANDTE CHEMIE-INTERNATIONAL EDITION 50 3 680 - 683 2011年 [査読有り][通常論文]
- Takahiro Suzuki, Susumu KobayashiORGANIC LETTERS 12 13 2920 - 2923 2010年07月 [査読有り][通常論文]
A concise synthesis of a highly functionalized chloropupukeananin (1) skeleton via a reverse electron-demand Diels-Alder reaction and intramolecular carbonyl-ene reaction sequence based on our proposed biosynthetic pathway is described. - Kazuma Tsuboi, Tomoaki Nakamura, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiTETRAHEDRON LETTERS 51 14 1876 - 1879 2010年04月 [査読有り][通常論文]
A second-generation total synthesis of (-)-diversifolin has been achieved by a more straightforward strategy. involving a highly stereochemistry-dependent 10-membered ring-closing metathesis and a stereoselective dihydroxylation/lactone transposition sequence. Compared to Our previous synthesis, the present synthesis is improved in the yield of the key intermediate 2 (20% in 12 steps from diol 8). (C) 2010 Elsevier Ltd. All rights reserved. - Ryosuke Matsui, Kentaro Seto, Kazuhiro Fujita, Takahiro Suzuki, Atsuo Nakazaki, Susumu KobayashiANGEWANDTE CHEMIE-INTERNATIONAL EDITION 49 52 10068 - 10073 2010年 [査読有り][通常論文]
- Shuhei Yamakoshi, Nobuyuki Hayashi, Takahiro Suzuki, Masahisa NakadaTETRAHEDRON LETTERS 50 38 5372 - 5375 2009年09月 [査読有り][通常論文]
This Letter describes the asymmetric total synthesis of (+)-carneic acid A via the stereoselective IMDA reaction of (E,E,E)-triene, which was prepared from the commercially available methyl (S)-3-hydroxy-2-methylpropionate. By this asymmetric total synthesis, we verified that the reported absolute structure of naturally occurring carneic acid A must be revised. (C) 2009 Elsevier Ltd. All rights reserved. - Natsumi Tanaka, Takahiro Suzuki, Takehiko Matsumura, Yosuke Hosoya, Masahisa NakadaANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 14 2580 - 2583 2009年 [査読有り][通常論文]
- K. C. Nicolaou, Stephen M. Dalby, Shuoliang Li, Takahiro Suzuki, David Y-K. ChenANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 41 7616 - 7620 2009年 [査読有り][通常論文]
- Nobuyuki Hayashi, Takahiro Suzuki, Kenji Usui, Masahisa NakadaTETRAHEDRON 65 4 888 - 895 2009年01月 [査読有り][通常論文]
This manuscript describes an alternative synthetic approach for (+)-phomopsidin, which shows strong inhibitory activity against the assembly of microtubule proteins. We observed that the TADA reaction of the macrolactone 5 with the reversed C11 configuration provided the desired cycloadduct 6 in 86% yield with excellent stereoselectivity (dr=16:1). Luche reduction of the ketone derived froth the major product of the TADA reaction resulted in a 91% yield with excellent stereoselectivity (dr=21:1), and the major product was Successfully converted to the known compound in the previously reported total synthesis of (+)-phomopsidin, thereby accomplishing the formal total synthesis of (+)-phomopsidin. (C) 2008 Elsevier Ltd. All rights reserved. - K. C. Nicolaou, Michael O. Frederick, Antonio C. B. Burtoloso, Ross M. Denton, Fatima Rivas, Kevin P. Cole, Robert J. Aversa, Romelo Gibe, Taiki Umezawa, Takahiro SuzukiJOURNAL OF THE AMERICAN CHEMICAL SOCIETY 130 23 7466 - 7476 2008年06月 [査読有り][通常論文]
As the largest secondary metabolite to be discovered as of yet, the polyether marine neurotoxin maiitotoxin constitutes a major structural and synthetic challenge. After its originally proposed structure (1) had been questioned on the basis of biosynthetic considerations, we provided computational and experimental support for structure 1. In an effort to provide stronger experimental evidence of the molecular architecture of maitotoxin, its GHIJKLMNO ring system 21 was synthesized. The (13)C NMR chemical shifts of synthetic 3 matched closely those corresponding to the same domain of the natural product providing strong evidence for the correctness of the originally proposed structure of maitotoxin (1). - Masahiro Inoue, Takahiro Suzuki, Akihiro Kinoshita, Masahisa NakadaCHEMICAL RECORD 8 3 169 - 181 2008年 [査読有り][通常論文]
Nozaki-Hiyama reactions are powerful Cr-II-mediated C-C bond-forming reactions conducted under mild conditions that show excellent compatibility with various functional groups. Therefore, Nozaki-Hiyama reactions have been utilized for many total syntheses of complex natural products, but at least two equivalents of Cr-II salt are required to complete the reaction because Cr-II salt is a one-electron donor. In 1996, however, the quantity of Cr-II salts required was successfully reduced by a catalytic redox system reported by Furstner and Shi. Since the report by Furstner, the catalytic asymmetric Nozaki-Hiyama reactions have attracted attention because they would allow control over enantioselectivity, thereby further enhancing the versatility of Nozaki-Hiyama reactions. In this review, we describe the development of a tridentate bis(oxazolinyl)carbazole ligand for the catalytic asymmetric Nozaki-Hiyama allylation, methallylation, propargylation, and allenylation. Also described are their successful applications to the highly stereoselective construction of the side chain of calcitriol lactone, as well as structure elucidation and the enantioselective first total synthesis of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, FR901512 and FR901516. (C) 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. - Natsumi Tanaka, Takahiro Suzuki, Yosuke Hosoya, Masahisa NakadaTETRAHEDRON LETTERS 48 37 6488 - 6492 2007年09月 [査読有り][通常論文]
Construction of the ABCD ring system of (-)-FRI 82877 via the intramolecular Diels-Alder (IMDA) reaction and the highly diastereoselective intramolecular hetero-Diels-Alder (IMHDA) reaction is described. The IMHDA reactions of the substrates incorporating the oxabutadiene with the E- or Z-alkene were examined, revealing that the sole product was obtained from both substrates and the E-alkene geometry was found to be crucial to obtaining the desired product. (c) 2007 Elsevier Ltd. All rights reserved. - Takahiro Suzuki, Natsumi Tanaka, Takehiko Matsumura, Yosuke Hosoya, Masahisa NakadaTETRAHEDRON LETTERS 48 37 6483 - 6487 2007年09月 [査読有り][通常論文]
Construction of the ABCD ring system of (-)-FR182877 via the highly diastereoselective intramolecular Diels-Alder (I MDA) reaction is described. The IMDA reaction of the oj-unsaturated aldehyde generated in situ from the corresponding acetal successfully provided the desired product 14 possessing the AB ring system as the single diastereomer. The CD ring system was constructed by the subsequent IMHDA reaction and the additional experiment suggested that the diastereoselectivity of the IMHDA reaction could be related to the EIZ geometry of alkene 17, which was generated in situ from 16. (c) 2007 Elsevier Ltd. All rights reserved. - T Suzuki, N Tanaka, T Matsumura, Y Hosoya, M NakadaTETRAHEDRON LETTERS 47 10 1593 - 1598 2006年03月 [査読有り][通常論文]
The structure-diastereoselectivity relationships in the IMDA reactions of the terminally activated (EEE)-nona-1,6,8-trienes have been studied. It is found that the configuration of the C3 position bearing the protected hydroxyl group is crucial to the diastereoselectivity, and the magnitude of the ratio depends on the relative configuration of the C3-C5 positions. The results obtained in this study including the new successful IMDA reactions would be useful for the stereoselective synthesis of natural products containing a bicyclo[4.3.0]non-2-ene carbon skeleton. (c) 2006 Elsevier Ltd. All rights reserved. - T Suzuki, K Usui, Y Miyake, M Namikoshi, M NakadaORGANIC LETTERS 6 4 553 - 556 2004年02月 [査読有り][通常論文]
The first total synthesis of (+)-phomopsidin has been achieved via a diastereoselective transannular Diels-Alder (TADA) reaction. Key steps in the synthesis include diastereoselective ynone reduction with (-)-alpha-pinene and 9-BBN, macrocyclization by E-selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction, as well as carbometalation under Wipf's conditions, followed by HWE reaction at low temperature to selectively construct the (E)-1-methylpropenyl and (1E,2E)-4-carboxy-1,3-butadienyl substituents. - T Suzuki, A Kinoshita, H Kawada, M NakadaSYNLETT 4 570 - 572 2003年03月 [査読有り][通常論文]
The manuscript describes our studies on a newly designed tridentate ligand. The new ligand 1 was successfully synthesized, and it was found that the asymmetric catalysis of Nozaki-Hiyama allylation with ligand 1 affords the product with good enantioselectivity in high yield. - M Inoue, T Suzuki, M NakadaJOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 5 1140 - 1141 2003年02月 [査読有り][通常論文]
- T Suzuki, M NakadaTETRAHEDRON LETTERS 43 18 3263 - 3267 2002年04月 [査読有り][通常論文]
An asymmetric synthesis of the AB ring moiety of FR182877. possessing semen asymmetric centers. via a diastereoselective IMDA reaction is described, (C) 2002 Elsevier Science Ltd. All rights reserved.
書籍
- 有機合成実験法ハンドブック第2版小林進, 鈴木孝洋 (担当:共著範囲:16章 アルドール反応)
丸善出版 2015年11月 - 有機合成実験法ハンドブック 第2版鈴木孝洋 (担当:共編者(共編著者)範囲:15 官能基の保護と脱保護)
丸善出版 2015年11月 (ISBN: 9784621089484) 1166 315-357
講演・口頭発表等
- 新規香料化合物の創製に向けたジバレラン骨格の改良合成法の開発 [通常講演]岡本ゆきの, 和田善行, 村西修一, 鈴木孝洋, 谷野圭持第62回香料・テルペンおよび精油化学 2018年10月 口頭発表（一般）
- Total Synthesis of Atropurpuran [通常講演]鈴木孝洋, 中西健太, 古山岳史, 小林進, 谷野圭持22nd International Conference on Organic Synthesis (22-ICOS) 2018年09月 口頭発表（一般）
- アトロプルプランの不斉全合成研究 [通常講演]古山岳史, 鈴木孝洋, 谷野圭持第53回天然物化学談話会 2018年07月 ポスター発表
- ヘチダン型ジテルペンの 収束的骨格構築法の開発 [通常講演]池田航, 鈴木孝洋, 谷野圭持第53回天然物化学談話会 2018年07月 ポスター発表
- ent-カウレンジテルペノイドKamebaninの全合成研究 [通常講演]菅野彩夏, 鈴木孝洋, 谷野圭持日本化学会第98春季年会 2018年03月 口頭発表（一般）
- 3-ヒドロキシ-2-ピロンを用いた新規[4+3]付加環化反応の開発 [通常講演]柳澤尚宗, 鈴木孝洋, 谷野圭持日本化学会第98春季年会 2018年03月 口頭発表（一般）
- 特異な構造の天然物の全合成と拡散的研究展開 [招待講演]鈴木孝洋化学系学協会北海道支部2018年冬季研究発表会 2018年01月 口頭発表（招待・特別）
- アトロプルプランの全合成 [通常講演]鈴木孝洋第 59 回天然有機化合物討論会 2017年09月 口頭発表（一般）
- 付加環化反応を基盤とした特異な環構造を有するテルペノイドの全合成研究 [招待講演]鈴木孝洋第61回香料・テルペンおよび精油化学 2017年09月 口頭発表（招待・特別）
- Enantioselective Total Synthesis of (+)-iso-A82775C [招待講演]鈴木孝洋International Symposium on Pure & Applied Chemistry (ISPAC) 2017 2017年06月 口頭発表（招待・特別）
- アトロプルプランの全合成 [通常講演]中西健太, 鈴木孝洋, 小林進, 谷野圭持日本化学会第97春季年会 2017年03月 口頭発表（一般）
- iso-A82775Cの不斉全合成 [通常講演]渡邉壮一郎, 鈴木孝洋, 谷野圭持日本化学会第97春季年会 2017年03月 口頭発表（一般）
- アイボレノイドAの全合成研究 [通常講演]堀口耕作, 鈴木孝洋, 谷野圭持第60回香料・テルペンおよび精油化学 2016年10月 口頭発表（一般）
- 連続的環化反応を利用したent-カウレン類の合成研究 [通常講演]菅野彩夏, 鈴木孝洋, 谷野圭持第60回香料・テルペンおよび精油化学 2016年10月 口頭発表（一般）
- Studies toward the Biomimetic Total Synthesis of Chloropupukeananin [招待講演]Takahiro Suzuki, Susumu Kobayashi, Keiji Tanino11th International Conference on Cutting-Edge Organic Chemistry in Asia 2016年10月 ポスター発表
- iso-A82775Cの全合成研究 [通常講演]渡邉壮一郎, 鈴木孝洋, 谷野圭持日本化学会北海道支部2016年夏季研究発表会 2016年07月 口頭発表（一般）
- iso-A82775Cの全合成研究 [通常講演]渡邉壮一郎, 鈴木孝洋, 谷野圭持第51回天然物化学談話会 2016年07月 ポスター発表
- ジバレラン骨格を有する新規香料化合物の創製とその香気特性 [通常講演]和田善行, 鈴木孝洋, 吉田啓, 鈴木真也, 中西健太, 佐久間克也, 作田圭亮, 谷野圭持, 清水功雄日本農芸化学会2016年度大会 2016年03月 ポスター発表
- Construction of Cage-like Tricyclic Skeleton of Chloropupukeananin, an Inhibitor of HIV-1 Replication [招待講演]Takahiro Suzuki, Susumu Kobayashi, Keiji Tanino4th International Postgraduate Conference on Pharmaceutical Science 2016年02月 口頭発表（招待・特別）
その他活動・業績
- 池内和忠, 原口翔太, 藤井りょう, 山田英俊, 鈴木孝洋, 谷野圭持 次世代を担う有機化学シンポジウム講演要旨集 21st 2023年
- 志村 聡美, 石間 正浩, 太田 育恵, 筒井 悦子, 紙透 伸治, 村田 寛, 山崎 隆之, 鈴木 孝洋, 倉持 幸司, 竹内 倫文, 小林 進, 菅原 二三男 天然有機化合物討論会講演要旨集 55 (0) 2013年 [査読無し][通常論文]
<p>【 背景 】</p><p>水産養殖の現場では、魚類病原ウイルスによる感染症の発生が水産資源の安定供給に深刻な影響を及ぼす。サケ科魚類の伝染性造血器壊死症ウイルス(Infectious hematopoietic necrosis virus : IHNV) はニジマス養殖に甚大な被害をもたらすが、同じ養殖池の中でもIHNVに耐性を示す個体と耐性を示さない個体がいた。両者の違いを調べると、前者では特定の細菌が消化管に生息していた。この細菌が生産し、抗ウイルス活性を示す物質としてMA026 (1) が単離された<sup>1)</sup>。MA026は当研究室で単離、構造決定された新規環状デプシペプチドであり、アミノ酸14残基からなる鎖環デプシペプチドに脂肪酸が結合した複雑な構造を有する (Figure 1)。本化合物はIHNVだけでなく、エンベロープを有する複数種のウイルスの増殖を抑制するが、その作用機序は解明されていない。本研究は、MA026の効率的な化学合成法の確立と標的分子の同定を目的とした。</p><p>【 合成戦略 】 </p><p>MA026はアミノ酸8残基からなるマクロラクトン構造に、アミノ酸6残基からなる鎖状ペプチド、N末端に (R)-3-ヒドロキシデカノイル基が結合した構造を有する。我々は、MA026を2つのセグメント2, 3に分割し、それぞれ合成した後縮合し、収束的に合成する計画を立案した (Scheme 1)。環状デプシペプチド3の合成では、アミド化に比べて反応性の低いエステル化を合成の早い段階で行うこととし、ペプチド主鎖の分岐構造を有する2つの環化基質4, 5を設定した。また、4と5は共通中間体ヘキサデプシペプチド6から導くこととした。6にテトラペプチドを縮合し、2行程で4 を合成したが、4の環化は進行しなかった<sup>2)</sup>。4の環化部位はD-Leu<sup>13</sup>-D-Val<sup>14</sup>であるが、2つの反応点の分岐からの距離が大きく異なるため、分子内マクロラクタム化が進行するにはより大きなコンフォメーション変化が必要になると予想された。一方、環化部位がD-Gln<sup>11</sup>-L-Leu<sup>12</sup>となる5では、2つの反応点の分岐からの距離はほぼ同じであり、4よりも環化しやすいと考えた。よって、3はデカデプシペプチド5の分子内マクロラクタム化により導くこととした。</p><p>【 デカデプシペプチド5の合成 】</p><p> </p><p>Alloc-L-Gln-OH (7) を出発原料とし、5行程でジペプチド9を合成した (Scheme 2)。また、MA026を構成する保護アミノ酸を調製し、それらを縮合し、脱保護することでジペプチド10、11、12、13を得た。次に9と10を縮合し、テトラペプチド14を得た (Scheme 3)。14のD-Ser側鎖ヒドロキシ基と11をエステル縮合することでヘキサデプシペプチド6 を合成した。6の有機溶媒に対する溶解性は高いが、ペプチド鎖の伸長と伴に溶解性の減少が観察された。ペプチドの溶解性を維持するためBCBを用いて6のTr基は除去せずBoc基を選択的に除去し、アミンとした。得られたアミンと12を縮合し、オクタデプシペプチド15を得た。次に15のBn基の脱保護を検討した。ジペプチド9の合成では (Scheme 2) THF溶媒中、Pd/Cを触媒とした加水素分解反応によりBn基のみを除去し、目的のカルボン酸を98%の収率で得ることができた。一方、15はTHFのような非プロトン性溶媒に難溶であり、MeOHを溶媒として加水素分解を行ったとこ</p><p>(View PDFfor the rest of the abstract.)</p> - 田中 遼, 大石 健太郎, 高梨 憲幸, 長野 智彦, 水津 拓, 鈴木 孝洋, 小林 進 天然有機化合物討論会講演要旨集 (54) 339 -344 2012年09月01日 [査読無し][通常論文]
In 2002, pyrrocidine A and B were isolated from the fermentation broth of a fungus, LL-Cyan 426, as antimicrobial agents against Gram-positive bacteria including drug-resistant strains. Structural features of pyrrocidines are tricyclic decahydrofluorene core (ABC-ring) and 13-membered macrocycle containing para-substituted aryl ether moiety. The complex molecular architecture of these compounds makes them very attractive target molecules for total synthesis. We report herein the stereoselective synthesis of decahydrofluorene 21 which provides the first entry to the ABC-ring moiety of pyrrocidines. The synthesis of 21 commenced with the construction of the C-ring moiety. The cyclic carbon skeleton was synthesized via Diels-Alder reaction between dimethyl-substituted Danishefsky-Yan diene 7 and trisubstituted alkene 8 to afford a diastereomeric mixture of cyclohexenone 10a-b. The ketone 11a possessing the desired configuration was mainly obtained by thermal epimerization of the diastereomeric mixture of 11a-c. Ring-closing metathesis reaction of diene 15, followed by Dess-Martin oxidation afforded the cyclic dienophile 16. Diels-Alder reaction between Danishefsky-Kitahara diene 5 and bicycloenone 16, and the sequential acidic treatment gave diketone 4, establishing the tricyclic carbon framework of 21. Owing to the inherent convex-face selectivity of cis-fused bicyclic AB-ring moiety of 4, nitrile 19 was stereoselectively synthesized in several steps. Vinyl group was introduced to 4 from concave face selectively, avoiding the adjacent cyano group, in two steps to afford ketone 20. The reduction of ketone group from convex face of 20, followed by Chugaev elimination furnished decahydrofluorene 21. - S. Shimura, M. Ishima, Ota, I, E. Tsutsui, S. Kamisuki, H. Murata, T. Yamazaki, T. Suzuki, K. Kuramochi, T. Takeuchi, K. Watashi, S. Kobayashi, F. Sugawara PLANTA MEDICA 78 (11) 1283 -1283 2012年08月 [査読無し][通常論文]
- 鈴木 孝洋, 佐々木 綾, 小林 進 天然有機化合物討論会講演要旨集 (53) 505 -510 2011年09月02日 [査読無し][通常論文]
In 2009, Wang and colleagues reported the isolation of a structurally unique non-alkaloidal diterpene, atropurpuran, from Aconitum hemsleyanum var. atropurpureum. The structure of atropurpuran features an unprecedented cage-like skeleton consisting of five six-membered rings. Intriguingly, B, C, D, and E ring constitute the tetracyclo[5.3.3.0^<4'9>.0^<4'12>]tridecane skeleton into which two bicyclo[2.2.2]octane are comprised. Despite of these biosynthetically and structurally intriguing properties of tetracyclo[5.3.3.0^<4'9>.0^<4'12>]tridecane skeleton, no synthetic effort has been reported so far. Herein, we report the first entry for the construction of tetracyclic skeleton and the pentacyclic carbon framework of atropurpuran via an intramolecular reverse electron-demand Diels-Alder (REDDA) reaction of masked o-benzoquinone (MOB). The preparation of REDDA precursor was started from o-eugenol 1. Tetralone 4 was successfully converted to ketone 7. Reduction of ketone 7 with DIBAL, silyl etherification, followed by oxidation with Phl(OAc)_2 afforded REDDA precursor 10d. The REDDA reaction of silyl ether 10d (180℃, 1h) afforded tetracyclic 11d in high yield almost as a single diastereomer. Next, we proceeded to the construction of pentacyclic skeleton toward the total synthesis of atropurpuran. Addition of allylmagnesium bromide to ketone 7, ring-closing metathesis gave tricyclic 15. Oxidation of tricyclic 15 with Phl(OAc)_2 and followed by REDDA reaction of resulting MOB was achieved to construct the pentacyclic 14. Finally, hydrogenation of 15 and subsequent dehydration (Tf_2O, pyridine) afforded 16 to complete the construction of the pentacyclic framework of atropurpuran. - 志村 聡美, 石間 正浩, 太田 育恵, 筒井 悦子, 紙透 伸治, 村田 寛, 山崎 隆之, 鈴木 孝洋, 倉持 幸司, 竹内 倫文, 小林 進, 菅原 二三男 天然有機化合物討論会講演要旨集 (53) 667 -672 2011年09月02日 [査読無し][通常論文]
MA026, a novel lipocyclodepsipeptide, exhibits selective antiviral activity against enveloped viruses such as influenza and herpes. An antiviral compound with complex depsipeptide structure like MA026 is scarce, and MA026 has the potential to inhibit viral infections with a novel mechanism. However, the availability of MA026 from natural resources is limited, therefore, the chemical synthesis is essential to accomplish the biological investigation. Here, we present synthetic studies to establish an efficient synthetic pathway to MA026. MA026 consists of (3R)-hydroxydecanoic acid, linear peptide six amino acids and cyclodepsipeptide eight amino acids. Nine of the amino acids posses the D-configuration. The retrosynthetic analysis of MA026 (1) is shown in Figure 2. MA026 was devided into three key segments to maximize the convergency : branched cyclic depsipeptide 2, tripeptide 3 and fatty acid moiety 4. Key to the total synsthesis of MA026 is the macrocyclization of depsipeptide, so we chose two macrocyclization sites, (A) D-Val - D-Leu and (B) L-Leu - D-Gln. Protected amino acids were condensed to gave tripeptide 3. Fatty acid moiety 4 was synthesized from n-octylaldehyde through samarium mediated Reformatsky reaction. The macrocyclization substrate 5 was prepared by the condensation of peptide fragments. Then, 5 was cyclized and the formation of branched cyclic peptide 2 was confirmed by mass spectorometry, however, the 2 was not obtained as a single compound. Five dipeptides were condensed to gave the macrocyclization substrate 6. Attempts to cyclize the precursor 6 is in progress. - 野崎 絵美, 後藤 真里, 堀田 晴美, 花澤 修和, 鈴木 孝洋, 小林 進, 室伏 きみ子 脂質生化学研究 53 264 -266 2011年04月28日 [査読無し][通常論文]
- 松井亮介, 瀬戸健太郎, 佐藤優奈, 藤田和弘, 鈴木孝洋, 中崎敦夫, 小林進 日本化学会講演予稿集 91st (4) 2011年
- 高梨憲幸, 田村圭司, 邊見和輝, 鈴木孝洋, 中崎敦夫, 小林進 反応と合成の進歩シンポジウム講演要旨集 37th 2011年
- Design and synthesis of molecular probe for identifying intracellular protein targetAya Toizaki, Aiko Suzuki, Atsuo Nakazaki, Takahiro Suzuki, Yoichi Takakusagi, Fumio Sugawara, Kengo Sakaguchi, Susumu Kobayashi International Symposium on Technologies against Cancer (ISTC2011) 2011年 [査読無し][通常論文]
- 高梨 憲幸, 田村 圭司, 邊見 和輝, 鈴木 孝洋, 中崎 敦夫, 小林 進 反応と合成の進歩シンポジウム 発表要旨概要 37 (0) 77 -77 2011年 [査読無し][通常論文]
A spiroiridal triterpenoid, 28-Deacetylbelamcandal was isolated from the rhizomes of <I>Belamcanda chinensis</I> in 1991. This natural product possesses a spiro[4.5]decane framework including five contiguous stereogenic centers and a tetrasubstituted olefin.<BR>Our strategy towards 28-Deacetylbelamcandal features Claisenrearrangement in alkenyl dihydropyran system for construction of a highly functionalized spiro[4.5]decane framework and stereoselective synthesis of tetrasubstituted olefin via intramolecular Heck reaction, subsequent deprotonation at bisallylic position and Rubottom oxidation.<BR>Alkenyl dihydropyran was prepared in 8 steps involving asymmetric aldol reaction and acid-catalyzed cyclization. The Claisen rearrangement (in triglyme, 0.05 M, 230 <SUP>o</SUP>C, 4 hr.) gave the desired product in 84% yield. Conversion of the Claisen product to the precursor for Heck reaction is currently under way. - 鈴木 孝洋, 宮嶋 ゆりあ, 鈴木 要, 小清水 正樹, 小林 進 反応と合成の進歩シンポジウム 発表要旨概要 37 (0) 51 -51 2011年 [査読無し][通常論文]
Chloropupukeananin (<B>1</B>) was isolated from <I>Pestalotiopsis fici</I> by Che and colleagues as a new inhibitor against HIV-1 replication. The array of functional groups in a rigid tricyclic structure of <B>1</B> has provided us with a strong motive to construct the pupukeanane core based on biosynthetic hypothesis. We proposed a biosynthetic pathway for chloropupukeananin via maldoxin involving a reverse electron-demand Diels-Alder (REDDA) reaction and an intramolecular carbonyl-ene reaction. Herein, we report the investigation of REDDA and carbonyl-ene reaction with a model of maldoxin and vinylallene.<BR>The precursors of REDDA were subjected to high pressure conditions to give a major product and other isomers. The X-ray crystallographic analysis of the major product revealed that the precursors underwent the REDDA reaction and the intramolecular carbonyl-ene reaction to construct the pupukeanane core in a single operation. - 松井 亮介, 瀬戸 健太郎, 佐藤 優奈, 藤田 和弘, 鈴木 孝洋, 中崎 敦夫, 小林 進 天然有機化合物討論会講演要旨集 (52) 13 -18 2010年09月01日 [査読無し][通常論文]
We have previously developed a highly stereoselective vinylogous Mukaiyama aldol reaction (VMAR) usin gvinylketene silyl N,O-acetal 1, which provides a unique and remarkable entry to a remote asymmetric induction. From a synthetic point of view, this method can directly afford th anti-δ-hydroxy-α,γ-dimethol-α,β-unsaturated carbonyl unit, which is seen in many naturally occurring products. In fact, VMAR has successfully been utilized in the total syntheses of various biologically active compounds by many groups including us. Se envisioned that the VMAR would be an efficient and powerful methodology for the synthesis of (+)-TMC-151C (2). This compound was isolated from Gliocladium sp. by the research group of Tanabe Seiyaku in 1999, and it shows the cytotoxicity to wide-rangingg tumor cell lines, such as HCT-116, B16 and HeLa. The structural significance as well as the biological property has stimulated the synthesis of TMC-151C (2). Herein, we report the first total synthesis of (+)-TMC-151C (2) using VMAR and Ring-Closing Metathesis (RCM) via a highly convergent synthetic route. Characteristic features of the present synthesis include: 1) the construction of C_1-C_5 segmetn and C_9-C_<13> segment was successfully achieved by VMAR, and 2) the stereoselective formation of C_6-C_7 double bond was accomplished by developing a unique E-olefin forming 8-membered RCM of silicon-tethered diene. Moreover, we observed a unique E-olefin forming 8-memberes ring RCM of silylene acetals, and proposed a plausible transition state as well as the structural requirement for E-olefin forming RCM. Although the E-olefin was produced only in a limited case, this methodology was quite useful for the total synthesis of TMC-151C (2). - 皆迫洋平, 山下大輔, 中崎敦夫, 鈴木孝洋, 小林進 日本薬学会年会要旨集 130th (2) 2010年
- 田中遼, 加藤賢, 後藤真里, 野崎絵美, 花澤修和, 中崎敦夫, 鈴木孝洋, 室伏きみ子, 小林進 日本薬学会年会要旨集 130th (2) 2010年
- 山下大輔, 皆迫洋平, 中島雄大, 中崎敦夫, 鈴木孝洋, 小林進 次世代を担う有機化学シンポジウム講演要旨集 8th 2010年
- 中島雄大, 山下大輔, 鈴木要, 中崎敦夫, 鈴木孝洋, 日景尚睦, 小林進 複素環化学討論会講演要旨集 40th 2010年
- 細井勇人, 河井伸之, 萩原秀樹, 鈴木孝洋, 中崎敦夫, 小林進 有機合成シンポジウム講演要旨集 98th 2010年
- 齊藤洋平, 中崎敦夫, 鈴木孝洋, 小林進 日本薬学会年会要旨集 130th (2) 2010年
- 高草木香織, 鈴木愛こ, 高草木洋一, 渡辺まどか, 松本勇記, 戸井崎絢, 鈴木孝洋, 中崎敦夫, 菅原二三男, 坂口謙吾 生化学 2010年
- 戸井崎 絢, 鈴木 愛こ, 中崎 敦夫, 鈴木 孝洋, 高草木 洋一, 菅原 二三男, 坂口 謙吾, 小林 進 反応と合成の進歩シンポジウム 発表要旨概要 36 (0) 44 -44 2010年 [査読無し][通常論文]
We attempted an identification of the molecular target of an antibiotic roxithromycin (RXM) using a T7 phage display (PD) screen on a quartz-crystal microbalance (QCM) device (QCM-PD). Wherein, we synthesized a RXM derivative that forms a self-assembled monolayer (SAM) for a specific RXM immobilization on the gold electrode surface of a QCM sensor chip. We then performed a one-cycle selection of RXM-binding peptides from a library of T7 phage-displayed peptides. As a result, we obtained 25 of RXM-recognizing sequences. Subsequent analysis utilizing the subset of sequence and receptor ligand contacts (RELIC) software clearly pinpointed several amino-acid residues within the RXM-binding site on the well-known direct targets, CYP3A4. Our findings demonstrate the effectiveness of this methodology and general applicability for a wide range of small-molecules. We are currently searching for another target responsible for anti-angiogenic effect of RXM. - 佐々木 綾, 鈴木 孝洋, 小林 進 反応と合成の進歩シンポジウム 発表要旨概要 36 (0) 38 -38 2010年 [査読無し][通常論文]
Atropurpuran was isolated from the roots of <I>Aconitum hemsleyanum var. atropurpureum</I> in 2009. Structurally, atropurpuran possesses an unprecedented skeleton, bis-bicyclo[2.2.2]octane, that includes a quaternary carbon shared with six six-membered rings.<BR>At the outset of our synthetic investigation on atropurpuran, we initially attempted to establish an efficient methodology for constructing a tetracyclic cage sketlon by employing an intramolecular reverse electron-demand Diels-Alder (REDDA) reaction. The preparation of REDDA precursor, having both MOB moiety and dienophile side chain, was achieved in 11 steps from guaiacol.<BR>The REDDA reaction of triene (in mesitylene, 180<SUP>o</SUP>C, 1 h) produced the desired cycloadduct in 77% yield. The structure of the cycloadduct was confirmed by NMR spectroscopy. - 佐藤優奈, 野中美穂, 鈴木孝洋, 中崎敦夫, 小林進 日本薬学会関東支部大会講演要旨集 53rd 2009年
- 松井亮介, 瀬戸健太郎, 藤田和弘, 中崎敦夫, 鈴木孝洋, 小林進 有機合成シンポジウム講演要旨集 96th 2009年
- 細井 勇人, 河井 伸之, 萩原 秀樹, 鈴木 孝洋, 中崎 敦夫, 小林 進 反応と合成の進歩シンポジウム 発表要旨概要 35 (0) 15 -15 2009年 [査読無し][通常論文]
Akaterpin, a specific inhibitor of PI-specific PLC, consists of two decalin rings and a hydroquinone disulfate moiety. Relative stereochemistry of each decalin moiety was determined dependently, and, therefore, relative structure has not been yet determined. Our strategy to akaterpin was to construct the upper decalin first, and construct the lower dacalin by intramolecular Diels-Alder reaction. The resulting two isomers were separated, and each isomer was transformed to the target molecule. We found that the H-NMR spectrum of the target molecule (racemic) derived from the major isomer of Diels-Alder reaction was found to be identical to that of natural akaterpin. Thus, we were able to achieve a total synthesis of akaterpin (racemic) and determine the relative stereochemistry. - 田中 奈津美, 鈴木 孝洋, 松村 岳彦, 細谷 洋介, 中田 雅久 天然有機化合物討論会講演要旨集 (50) 239 -244 2008年09月01日 [査読無し][通常論文]
(-)-FR182877 was isolated from the fermentation broth of Streptomyces sp. No. 9885 by a research group of Fujisawa Pharmaceutical Company in 1998. This compound possesses an unprecedented hexacyclic ring system containing a bridgehead double bond as part of a vinylogous carbonate unit and 12 stereogenic centers, and exhibits microtubule stabilizing activity similar to that of Taxol. Hence, the complex structure and promising bioactivity of (-)-FR182877 have attracted considerable attention from synthetic chemists. Our synthetic approach began with the conversion of known aldehyde 8 to precu... - Tanaka Natsumi, Suzuki Takahiro, Hosoya Yosuke, Nakada Masahisa International Symposium on the Chemistry of Natural Products 2006 "P -453" 2006年07月23日
- T Suzuki, T Matsumura, N Tanaka, M Nakada ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 229 U514 -U514 2005年03月 [査読無し][通常論文]
- T Suzuki, K Usui, Y Miyake, M Namikoshi, M Nakada ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 229 U513 -U513 2005年03月 [査読無し][通常論文]
- 鈴木 孝洋, 三宅 祥元, 臼井 研二, 中田 雅久, 浪越 通夫 天然有機化合物討論会講演要旨集 (45) 545 -550 2003年09月01日 [査読無し][通常論文]
Phomopsidin was isolated from Phompsis sp. TUF95F47 by Namikoshi and co-workers in 1997, and its absolute structure and biological activity have been reported. Phomopsidin and its geometrical isomer (MK8383) showed potent inhibitory activity against assembly of microtubule proteins, exhibiting strong antitumor activity. It has been proposed that phomopsidin could be generated via the IMDA reaction of 1. Therefore, the potent antitumor activity and this biosynthetic background draw our attention to the synthesis of phomopsidin. We planned to synthesize the cis-decalin core 2 of phomopsidin f... - 井上 雅大, 鈴木 孝洋, 中田 雅久 反応と合成の進歩シンポジウム 発表要旨概要 29 (0) 210 -211 2003年 [査読無し][通常論文]
二価のクロム塩を用いた炭素–炭素結合形成反応（野崎–檜山反応）は、その高い官能基選択性、立体選択性から非常に有用であり、多くの天然物の全合成に適用されてきた。しかし、野崎–檜山反応の不斉触媒化の報告例は少なく、そのエナンチオ選択性も満足いくものではなかった。そこで我々は新規の不斉配位子をデザイン、合成し、触媒的不斉野崎–檜山アリル化反応を検討した。<sup>1)</sup>カルバゾールを原料とし５行程で不斉配位子の合成に成功した。この配位子を用いて野崎–檜山アリル化反応をおこなったところ、アルデヒドの種類によらず高エナンチオ選択にホモアリルアルコールを得ることに成功した（86–95% ee）。<sup>2)</sup>またメタリル化についても一般性が見られた(90–96% ee)。興味深いことに、このクロムと不斉配位子との錯体は空気や水に対して安定であり、繰り返し触媒反応を行うことが可能であった。その際、生成物のエナンチオ選択性に低下は見られなかった。さらに、本反応の天然物合成への適用例も併せて報告する。
受賞
- 2018年01月 日本化学会北海道支部 日本化学会北海道支部奨励賞
特異な構造の天然物の全合成と拡散的研究展開受賞者: 鈴木孝洋 - 2016年10月 Asian Core Program Lectureship Award from HongKong
受賞者: 鈴木孝洋 - 2016年10月 Asian Core Program Lectureship Award from China
受賞者: 鈴木孝洋
共同研究・競争的資金等の研究課題
- 日本学術振興会：科学研究費助成事業 基盤研究(C)研究期間 : 2020年04月 -2023年03月代表者 : 鈴木 孝洋立体的に複雑な縮環構造（高次構造）を有する天然有機化合物（天然物）は、有用な生物活性を示すものが多く、医薬品・農薬として利用されてきた。それらの多くは有機化学的に合成されているが、依然として合成未達成のものも残されている。申請者の提案する「一段階多重環構築戦略」は、これらの合成困難な高次構造天然物に対する有効なアプローチであると考えている。そこで本研究では、近年シキミ属植物から単離が報告されたイリシモニンAを標的化合物とし、全合成を達成することで「一段階多重環構築戦略」の有用性を実証することにした。 昨年度に引き続き、イリシモニンAの骨格合成に向けてモデル化合物を用いた検討を行った。アロセドラン骨格からイリシモニンA骨格への骨格転位反応は、当初ベンジル酸転位による反応機構で進行すると推定していたが、詳細な反応条件の検討の結果、レトロクライゼン反応/アルドール反応の二段階の反応によって起きていることを明らかにした。これにより全合成達成には、ビシクロ[2.2.2]オクタン上の3つのケト基が必須であることが判明した。しかしながら、レトロクライゼン反応/アルドール反応によって生じるα-ヒドロキカルボン酸は望みでない立体化学の異性体が優先して得られているため、選択性の改善が今後の課題である。 現在イリシモニンAの全合成に向けて、すべての必要な官能基を備えた基質をもちいた合成に着手し、アロセドラン骨格の合成段階を検討している。
- 日本学術振興会：科学研究費助成事業 基盤研究(B)研究期間 : 2010年 -2012年代表者 : 小林 進, 鈴木 孝洋キラルイミドを不斉補助基として用いるジアステレオ選択的反応は、複雑な骨格を有する標的分子の不斉合成において重要な手段として国内外で活用されている。本研究では本申請者がこれまでに開発した二種類のアルドール型反応に関し、(1)ビニロガス向山アルドール反応の改善、(2)不斉3級アルコールを含む1,2-ジオールの立体選択的合成法については、基質一般性の検討、(3)これらの方法論を活用した生物活性天然物の不斉合成への応用を行った。