2023/09/21 更新

写真a

フワ ハルヒコ
不破 春彦
FUWA Haruhiko
所属
理工学部 教授
その他担当機関
理工学研究科応用化学専攻博士課程前期課程
理工学研究科応用化学専攻博士課程後期課程
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外部リンク

学位

  • 博士(理学) ( 東京大学 )

  • 修士(理学) ( 東京大学 )

学歴

  • 2002年3月
     

    東京大学   大学院理学系研究科   化学専攻   博士   修了

  • 1999年3月
     

    東京大学   大学院理学系研究科   化学専攻   修士   修了

  • 1997年3月
     

    東京大学   理学部   化学科   卒業

  • 1993年3月
     

    宮城県仙台第二高等学校   卒業

経歴

  • 2017年4月 -  

    中央大学理工学部 教授

  • 2009年5月 - 2017年3月

    東北大学大学院生命科学研究科 准教授

  • 2007年4月 - 2009年4月

    東北大学大学院生命科学研究科 助教

  • 2006年7月 - 2007年3月

    東北大学大学院生命科学研究科 助手

  • 2005年4月 - 2006年6月

    日本学術振興会特別研究員(PD)

  • 2005年2月 - 2005年3月

    東北大学大学院生命科学研究科 研究支援者

  • 2002年10月 - 2005年1月

    東京大学大学院薬学系研究科 寄付講座教員(助手相当)

  • 2001年4月 - 2002年9月

    日本学術振興会特別研究員(DC2)

▼全件表示

所属学協会

  • 日本薬学会

  • 日本化学会

  • 有機合成化学協会

  • 日本ケミカルバイオロジー学会

研究キーワード

  • 天然物有機化学

  • 有機合成化学

研究分野

  • ナノテク・材料 / 構造有機化学、物理有機化学  / 有機合成化学

  • ライフサイエンス / 生物有機化学  / 生物有機化学

  • ナノテク・材料 / 生物分子化学  / 生物分子化学

  • ライフサイエンス / 生物有機化学  / 有機合成化学

論文

  • Total Synthesis of (+)-Muricatetrocin B via a Late-Stage Co-Catalyzed Hartung–Mukaiyama Cyclization 査読

    Riko Minami, Tsubasa Kasai, Keisuke Murata, Haruhiko Fuwa

    Organic Letters   25   5745 - 5749   2023年8月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/acs.orglett.3c01932

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  • Au-catalyzed stereodivergent synthesis of 2,5-disubstituted pyrrolidines: total synthesis of (+)-monomorine I and (+)-indolizidine 195B 査読

    Hayato Nakagawa, Haruhiko Fuwa

    Chemical Communications   59   10121 - 10124   2023年7月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry (RSC)  

    A stereodivergent synthesis of 2,5-disubstituted pyrrolidines from readily available amino alkynes was made possible under Au catalysis.

    DOI: 10.1039/d3cc02453a

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  • Collective Asymmetric Total Synthesis of Cylindricines 査読

    R. Hanzawa, H. Fuwa

    Organic Letters   25   1984 - 1988   2023年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.orglett.3c00551

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  • An 11-Step Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy 査読

    Kazuki Nakazato, Mami Oda, Haruhiko Fuwa

    Bulletin of the Chemical Society of Japan   96   257 - 267   2023年2月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1246/bcsj.20220340

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  • GIAO NMR Calculation-driven Stereochemical Assignment of Marine Macrolide Natural Products: Assessment of the Performance of DP4 and DP4+ Analyses and Assignment of the Relative Configuration of Leptolyngbyalide A–C/Oscillariolide Macrolactone 査読

    Keisuke Murata, Hirotoshi Mori, Haruhiko Fuwa

    Bulletin of the Chemical Society of Japan   95 ( 12 )   1775 - 1785   2022年11月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Chemical Society of Japan  

    DOI: 10.1246/bcsj.20220253

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  • Stereoselective Tandem Synthesis of Pyrrolidine Derivatives under Gold Catalysis: An Asymmetric Synthesis of (−)-Lepadiformine A 査読

    A. Yoshimura, R. Hanzawa, H. Fuwa

    Organic Letters   24   6237 - 6241   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acs.orglett.2c02007

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  • Total Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy 査読

    K. Nakazato, M. Oda, H. Fuwa

    Organic Letters   24   4003 - 4008   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acs.orglett.2c01429

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  • Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells 査読

    E. Benoit, S. Schlumberger, J. Molgó, M. Sasaki, H. Fuwa, R. Bournaud

    Toxins   14   254   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI  

    DOI: 10.3390/toxins14040254

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  • Tandem Macrolactone Synthesis: Total Synthesis of (−)-Exiguolide by a Macrocyclization/Transannular Pyran Cyclization Strategy 査読

    D. Mizukami, K. Iio, M. Oda, Y. Onodera, H. Fuwa

    Angewandte Chemie, International Edition   61   e202202549   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

    DOI: 10.1002/anie.202202549

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  • Determination of the toxicity equivalency factors for ciguatoxins using human sodium channels 査読

    S. Raposo-Garcia, M. C. Louzao, H. Fuwa, M. Sasaki, C. Vale, L. Botana

    Food and Chemical Toxicology   160   112812   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.fct.2022.112812

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  • Asymmetric Synthesis of (−)-Atorvastatin Calcium by Tandem Catalysis 査読

    Keisuke Murata, Riko Minami, Haruhiko Fuwa

    Bulletin of the Chemical Society of Japan   94 ( 8 )   2028 - 2035   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Chemical Society of Japan  

    DOI: 10.1246/bcsj.20210178

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  • Ruthenium-Catalyzed Intramolecular Double Hydrofunctionalization of Alkynes. Synthesis of Spirocyclic Hemiaminal Ethers and Their Lewis Acid-Mediated Cleavage/Nucleophilic Addition 査読

    K. Nishimura, R. Hanzawa, T. Sugai, H. Fuwa

    The Journal of Organic Chemistry   86   6674 - 6697   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acs.joc.1c00443

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  • Stereoselective Synthesis of the Southern Hemisphere Acyclic Domain of Neaumycin B 査読

    H. Takeshita, T. Sugai, H. Fuwa

    The Journal of Organic Chemistry   86   6787 - 6799   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acs.joc.1c00508

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  • Cobalt-Catalyzed Hartung–Mukaiyama Cyclization of γ-Hydroxy Olefins: Stereocontrolled Synthesis of the Tetrahydrofuran Moiety of Amphidinolide N

    M. Ohta, S. Kato, T. Sugai, H. Fuwa

    The Journal of Organic Chemistry   86   5584 - 5615   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acs.joc.1c00085

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  • Total synthesis and complete configurational assignment of amphirionin-2 査読

    S. Kato, D. Mizukami, T. Sugai, M. Tsuda, H. Fuwa

    Chemical Science   12 ( 3 )   872 - 879   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:RSC  

    DOI: 10.1039/D0SC06021F

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  • Unified Total Synthesis of (–)-Enigmazole A and (–)-15-O-Methylenigmazole A 査読

    Keisuke Sakurai, Keita Sakamoto, Makoto Sasaki, Haruhiko Fuwa

    Chemistry - An Asian Journal   15   3494 - 3502   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

    DOI: 10.1002/asia.202001015

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  • Gambierol Potently Increases Evoked Quantal Transmitter Release and Reverses Pre- and Post-Synaptic Blockade at Vertebrate Neuromuscular Junctions 査読

    J. Molgo, S. Schulmberger, M. Sasaki, H. Fuwa, M. C. Louzao, L. M. Botana, D. Servent, E. Benoit

    Neuroscience   439   106 - 116   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.neuroscience.2019.06.024

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  • Tandem Three-Component Synthesis of syn-1,2- and syn-1,3-Diol Derivatives 招待 査読

    K. Murata, H. Takeshita, K. Sakamoto, H. Fuwa

    Chemistry - An Asian Journal   15 ( 6 )   807 - 819   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

    DOI: 10.1002/asia.201901660

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  • Total Synthesis, Stereochemical Revision, and Biological Assessment of Iriomoteolide‐2a 査読 国際誌

    K. Sakamoto, A. Hakamata, A. Iwasaki, K. Suenaga, M. Tsuda, H. Fuwa

    Chemistry - A European Journal   25 ( 36 )   8528 - 8542   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

    DOI: 10.1002/chem.201900813

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  • Fluorescence-labeled neopeltolide derivatives for subcellular localization imaging 査読 国際誌

    S. Yanagi, T. Sugai, T. Noguchi, M. Kawakami, M. Sasaki, S. Niwa, A. Sugimoto, H. Fuwa

    Organic & Biomolecular Chemistry   17 ( 28 )   6771 - 6776   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:RSC  

    DOI: 10.1039/C9OB01276A

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  • Stereoselective Tandem Synthesis of syn-1,3-Diol Derivatives by Integrating Olefin Cross-Metathesis, Hemiacetalization, and Intramolecular Oxa-Michael Addition 査読

    Keisuke Murata, Keita Sakamoto, Haruhiko Fuwa

    Organic Letters   21 ( 10 )   3730 - 3734   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/acs.orglett.9b01182

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  • Ruthenium-Catalyzed Intramolecular Double Hydroalkoxylation of Internal Alkynes 査読

    K. Iio, S. Sachimori, T. Watanabe, H. Fuwa

    Organic Letters   20   7851 - 7855   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:米国化学会  

    DOI: 10.1021/acs.orglett.8b03368

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  • Total Synthesis of (−)‐Enigmazole A 査読

    K. Sakurai, M. Sasaki, H. Fuwa

    Angewandte Chemie, International Edition   57 ( 18 )   5143 - 5146   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

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  • Total synthesis and stereochemical revision of iriomoteolide-2a 査読

    K. Sakamoto, A. Hakamata, M. Tsuda, H. Fuwa

    Angewandte Chemie, International Edition   57   3801 - 3805   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-VCH  

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  • A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells 査読

    Haruhiko Fuwa, Mizuho Sato

    MARINE DRUGS   15 ( 10 )   320   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells.

    DOI: 10.3390/md15100320

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  • Tetracyclic truncated analogue of the marine toxin gambierol modifies NMDA, tau, and amyloid β expression in mice brains: Implications in AD pathology 査読

    E. Alonso, A. C. Vieira, I. Rodriguez, R. Alvarino, S. Gegunde, H. Fuwa, Y. Suga, M. Sasaki, A. Alfonso, J. M. Cifuentes, L. M. Botana

    ACS Chemical Neuroscience   8 ( 6 )   1358 - 1367   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS  

    DOI: 10.1021/acschemneuro.7b00012

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  • (−)-Lyngbyaloside B, a Marine Macrolide Glycoside: Total Synthesis and Stereochemical Revision 査読

    H. Fuwa

    Strategies and Tactics in Organic Synthesis   12   143 - 168   2017年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Elsevier  

    DOI: 10.1016/B978-0-08-100756-3.00005-4

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  • Exploiting ruthenium carbene-catalyzed reactions in total synthesis of marine oxacyclic natural products 査読

    H. Fuwa, M. Sasaki

    Bulletin of the Chemical Society of Japan   89 ( 12 )   1403 - 1415   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本化学会  

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  • Diastereoselective Ring-Closing Metathesis as a Means to Construct Medium-Sized Cyclic Ethers: Application to the Synthesis of a Photoactivatable Gambierol Derivative 査読

    Yu Onodera, Kazuaki Hirota, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki, Haruhiko Fuwa

    JOURNAL OF ORGANIC CHEMISTRY   81 ( 18 )   8234 - 8252   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    This paper describes a concise synthesis of six- to eight-membered alpha,alpha'-substituted cyclic ethers by exploiting diastereoselective ring-closing metathesis (RCM) of 1,4-pentadien-3-yl ether derivatives. The RCM precursors could be efficiently prepared via a vinylation of the corresponding a-acetoxy ether derivatives using divinylzinc. Diastereoselective RCM of 1,4-pentadien-3-yl ether derivatives afforded a series of six- to eight-membered alpha,alpha'-substituted cyclic ethers with moderate to good diastereoselectivity. The stereochemical consequence of the diastereoselective RCM appeared to be dependent on the structure of the ring being forged. The diastereoselectivity of six- and seven-membered cyclic ethers appeared to be largely under kinetic control irrespective of the catalyst reactivity, whereas that of an eight-membered cyclic ether could be controlled by the catalyst reactivity. Finally, the diastereoselective RCM chemistry was applied to the synthesis of a biotin-tagged photoactivatable derivative of gambierol.

    DOI: 10.1021/acs.joc.6b01302

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  • Effect of carbon chain length in acyl coenzyme A on the efficiency of enzymatic transformation of okadaic acid to 7-O-acyl okadaic acid 査読

    Sachie Furumochi, Tatsuya Onoda, Yuko Cho, Haruhiko Fuwa, Makoto Sasaki, Mari Yotsu-Yamashita, Keiichi Konoki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   26 ( 13 )   2992 - 2996   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Okadaic acid (OA), a product of dinoflagellate Prorocentrum spp., is transformed into 7-O-acyl OA in various bivalve species. The structural transformation proceeds enzymatically in vitro in the presence of the microsomal fraction from the digestive gland of bivalves. We have been using LC-MS/MS to identify OA-transforming enzymes by detecting 7-O-acyl OA, also known as dinophysistoxin 3 (DTX3). However, an alternative assay for DTX3 is required because the OA-transforming enzyme is a membrane protein, and surfactants for solubilizing membrane proteins decrease the sensitivity of LC-MS/MS. The present study examined saturated fatty acyl CoAs with a carbon chain length of 10 (decanoyl), 12 (dodecanoyl), 14 (tetradecanoyl), 16 (hexadecanoyl) and 18 (octadecanoyl) as the substrate for the in vitro acylation reaction. Saturated fatty acyl CoAs with a carbon chain length of 14, 16 and 18 exhibited higher yields than those with a carbon chain length of 10 or 12. Acyl CoAs with carbon chain lengths from 14 to 18 and containing either a diene unit, an alkyne unit, or an azide unit in the carbon chain were synthesized and shown to provide the corresponding DTX3 with a yield comparable to that of hexadecanoyl CoA. The three functional units can be conjugated with fluorescent reagents and are applicable to the development of a novel assay for DTX3. (C) 2016 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2016.05.027

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  • Total synthesis and complete stereostructure of a marine macrolide glycoside, (–)-lyngbyaloside B 査読

    H. Fuwa, ほか

    Chemistry - A European Journal   22 ( 20 )   6815 - 6829   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/chem.201600341

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  • Complete Stereochemical Assignment of Campechic Acids A and B 査読

    Ruri Isaka, Linkai Yu, Makoto Sasaki, Yasuhiro Igarashi, Haruhiko Fuwa

    JOURNAL OF ORGANIC CHEMISTRY   81 ( 9 )   3638 - 3647   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Campechic acids A and B are anti-invasive polyketide antibiotics isolated from Streptomyces sp. CHI93 strain. Herein we describe stereoselective synthesis of the C-16-C-30 fragment of campechic acids A and B via a biosynthesis-inspired epoxide-opening cascade and its NMR spectroscopic comparison with the authentic degradation product, resulting in configurational assignment of the C-21, C-24, C-25, and C-28 stereogenic centers and reassignment of the C-18 stereogenic center.

    DOI: 10.1021/acs.joc.6b00290

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  • Toward the total synthesis of amphidinolide N: Convergent synthesis of the C8–C29 fragment 査読

    Y. Kawashima, A. Toyoshima, H. Fuwa, M. Sasaki

    Organic Letters   18 ( 9 )   2232 - 2235   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/acs.orglett.6b00871

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  • Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives: Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural Product 査読

    Haruhiko Fuwa

    MARINE DRUGS   14 ( 4 )   65   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Tetrahydropyrans are structural motifs that are abundantly present in a range of biologically important marine natural products. As such, significant efforts have been paid to the development of efficient and versatile methods for the synthesis of tetrahydropyran derivatives. Neopeltolide, a potent antiproliferative marine natural product, has been an attractive target compound for synthetic chemists because of its complex structure comprised of a 14-membered macrolactone embedded with a tetrahydropyran ring, and twenty total and formal syntheses of this natural product have been reported so far. This review summarizes the total and formal syntheses of neopeltolide and its analogues, highlighting the synthetic strategies exploited for constructing the tetrahydropyran ring.

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  • Progress toward the total synthesis of goniodomin A: Stereocontrolled, convergent synthesis of the C12–C36 fragment 査読

    H. Fuwa, ほか

    The Journal of Organic Chemistry   81 ( 6 )   2213 - 2227   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/acs.joc.5b02650

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  • Total synthesis, stereochemical revision, and biological evaluation of lyngbyaloside B, a marine macrolide glycoside

    H. Fuwa, Y. Okuaki, N. Yamagata, M. Sasaki

    Abstracts of PACIFICHEM2015   2015年12月

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    記述言語:英語   出版者・発行元:PACIFICHEM2015  

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  • Concise synthesis of the C15–C38 fragment of okadaic acid, a specific inhibitor of protein phosphatases 1 and 2A 査読

    H. Fuwa, K. Sakamoto, T. Muto, M. Sasaki

    Tetrahedron   71 ( 37 )   6369 - 6383   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.tet.2015.04.001

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  • Potassium currents inhibition by gambierol analogs prevents human T lymphocyte activation 査読

    J. A. Rubiolo, C. Vale, V. Martin, H. Fuwa, M. Sasaki, L. M. Botana

    ARCHIVES OF TOXICOLOGY   89 ( 7 )   1119 - 1134   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER HEIDELBERG  

    Gambierol is a marine polycyclic ether toxin, produced along with ciguatoxin congeners by the dinoflagellate Gambierdiscus toxicus. We have recently reported that two truncated skeletal analogs of gambierol comprising the EFGH- and BCDEFGH-rings of the parent compound showed similar potency to gambierol on voltage-gated potassium channels (Kv) inhibition in neurons. Gambierol and its truncated analogs share the main crucial elements for biological activity, which are the C28=C29 double bond within the H-ring and the unsaturated side chain. Since Kv channels are critical for the regulation of calcium signaling, proliferation, secretion and migration in human T lymphocytes, we evaluated the activity of both the tetracyclic and heptacyclic analogs of gambierol on potassium currents in resting T lymphocyte and their effects on interleukin-2 (IL-2) release and gene expression in activated T lymphocytes. The results presented in this work clearly demonstrate that both truncated analogs of gambierol inhibit Kv channels present in resting T lymphocytes (Kv1.3) and prevented lymphocyte activation by concanavalin A. The main effects of the heptacyclic and tetracyclic analogs of gambierol in human T cells are: (1) inhibition of potassium channels in resting and concanavalin-activated T cells in the nanomolar range, (2) inhibition of IL-2 release from concanavalin-activated T cells and (3) negatively affect the expression of genes involved in cell proliferation and immune response observed in concanavalin-activated lymphocytes. These results together with the lack of toxicity in this cellular model, indicates that both analogs of gambierol have additional potential for the development of therapeutic tools in autoimmune diseases.

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  • Evaluation of gambierol and its analogs for their inhibition of human K(v)1.2 and cytotoxicity 査読

    Keiichi Konoki, Yuto Suga, Haruhiko Fuwa, Mari Yotsu-Yamashita, Makoto Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   25 ( 3 )   514 - 518   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Gambierol and its heptacyclic and tetracyclic analogs were tested for inhibitory activity against the human voltage-gated potassium channel Kv1.2 (hKv1.2), which was stably expressed in Chinese hamster ovary (CHO) cells. Gambierol, the heptacyclic analog, and the tetracyclic analog inhibited the potassium current evoked by a step pulse from -80 mV to 40 mV. The IC50 values for the three compounds were 0.75 +/- 0.15 nM, 7.6 +/- 1.2 nM, and 28 +/- 4.0 nM (the mean +/- SEM, n = 3), respectively. The cytotoxic activity was examined in order to assess a relationship between cytotoxicity and inhibition of the hKv1.2. The IC50 values for gambierol, the heptacyclic analog, and the tetracyclic analog in the wild-type CHO cells were 95 +/- 7.1 lM, 6.5 +/- 0.8 lM(the mean +/- SEM, n = 3), and > 100 lM (n = 3), respectively, whereas those in the CHO cells stably expressing hKv1.2 were 78 +/- 5.8 lM, 6.0 +/- 1.0 lM (the mean +/- SEM, n = 3), and > 100 lM (n = 3). These results suggested that cytotoxicity is not triggered by inhibition of the human Kv1.2. The electrophysiological recording at the resting potential in the presence of gambierol, the heptacyclic analog, and the tetracyclic analog revealed the dose-dependent leak current, which was largest when the heptacyclic analog was administered to the cells. We thus propose that the leak current induced by these compounds might cause a fatal effect on the cultured cells. (C) 2014 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2014.12.022

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  • Concise synthesis of the C15–C38 fragment of okadaic acid: Application of Suzuki–Miyaura reaction to spiroacetal synthesis 査読

    H. Fuwa, K. Sakamoto, T. Muto, M. Sasaki

    Organic Letters   17 ( 2 )   366 - 369   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

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  • Concise synthesis of the A/BCD-ring fragment of gambieric acid A 査読

    Haruhiko Fuwa, Ryo Fukazawa, Makoto Sasaki

    FRONTIERS IN CHEMISTRY   2   116   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FRONTIERS MEDIA SA  

    Gambieric acid A (GAA) and its congeners belong to the family of marine polycyclic ether natural products. Their highly complex molecular architecture and unique biological activities have been of intense interest within the synthetic community. We have previously reported the first total synthesis, stereochemical reassignment, and preliminary structure activity relationships of GAA. Here we disclose a concise synthesis of the A/BCD-ring fragment of GAA. The synthesis started from our previously reported synthetic intermediate that represents the A/B-ring. The C-ring was synthesized via an oxiranyl anion coupling and a 6-endo cyclization, and the D-ring was forged by means of an oxidative lactonization and subsequent palladium-catalyzed functionalization of the lactone ring. In this manner, the number of linear synthetic steps required for the construction of the C- and D-rings was reduced from 22 to 11.

    DOI: 10.3389/fchem.2014.00116

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  • Total synthesis, stereochemical reassignment, and biological evaluation of (–)-lyngbyaloside B 査読

    H. Fuwa, Y. Okuaki, N. Yamagata, M. Sasaki

    Angewandte Chemie, International Edition   54 ( 3 )   868 - 873   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/anie.201409629

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  • Studies toward the total synthesis of amphidinolide N: Stereocontrolled synthesis of the C13–C29 segment 査読

    M. Sasaki, Y. Kawashima, H. Fuwa

    Heterocycles   90 ( 1 )   579 - 599   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本複素環化学研究所  

    DOI: 10.3987/COM-14-S(K)66

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  • Programmed cell death induced by (–)-8,9-dehydroneopeltolide in human promyelocytic leukemia HL-60 cells under energy stress conditions 査読

    H. Fuwa, M. Sato, M. Sasaki

    Marine Drugs   12 ( 11 )   5576 - 5589   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI  

    DOI: 10.3390/md12115576

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  • Synthetic and structural studies on lyngbyaloside B, a cytotoxic marine macrolide glycoside

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products   2014年10月

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    記述言語:英語   出版者・発行元:新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」  

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  • Total Synthesis and Complete Structural Assignment of Gambieric Acid A, a Large Polycyclic Ether Marine Natural Product 査読

    Makoto Sasaki, Haruhiko Fuwa

    CHEMICAL RECORD   14 ( 4 )   678 - 703   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    More than thirty years after the discovery of polycyclic ether marine natural products, they continue to receive intense attention from the chemical, biological, and pharmacological communities because of their potent biological activities and highly complex molecular architectures. Gambieric acids are intriguing polycyclic ethers that exhibit potent antifungal activity with minimal toxicity against mammals. Despite the recent advances in the synthesis of this class of natural products, gambieric acids remain unconquered due to their daunting structural complexity, which poses a formidable synthetic challenge to organic chemists. This paper reviews our long-term studies on the total synthesis, complete configurational reassignment, and structure-activity relationships of gambieric acid A over the last decade.

    DOI: 10.1002/tcr.201402052

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  • Synthesis and biological evaluation of (+)-neopeltolide analogues: Importance of the oxazole-containing side chain 査読

    Haruhiko Fuwa, Takuma Noguchi, Masato Kawakami, Makoto Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   24 ( 11 )   2415 - 2419   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    We describe the synthesis and biological evaluation of (+)-neopeltolide analogues with structural modifications in the oxazole-containing side chain. Evaluation of the antiproliferative activity of newly synthesized analogues against A549 human lung adenocarcinoma cells and PANC-1 human pancreatic carcinoma cells have shown that the C19-C20 and C26-C27 double bonds within the oxazole-containing side chain and the terminal methyl carbamate group are essential for potent activity. (C) 2014 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2014.04.031

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  • Stereoselective Synthesis of Medium-Sized Cyclic Ethers: Application of C-Glycosylation Chemistry to Seven- to Nine-Membered Lactone-Derived Thioacetals and Their Sulfone Counterparts 査読

    Yuto Suga, Haruhiko Fuwa, Makoto Sasaki

    JOURNAL OF ORGANIC CHEMISTRY   79 ( 4 )   1656 - 1682   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Stereoselective synthesis of alpha,alpha'-substituted medium-sized cyclic ethers has been achieved by means of nucleophilic substitution of the corresponding lactone-derived thioacetals and their sulfone counterparts. Nucleophilic substitution of medium-sized lactone-derived thioacetals could be achieved efficiently either by (i) activation with NIS/TMSOTf in the presence of allyltrimethylsilane or TMSCN or by (ii) oxidation to the corresponding sulfones followed by treatment with an appropriate organometallic species such as divinylzinc or dimethyl(2-phenylethynyl)aluminum. Interestingly, the stereochemical consequence was found to be largely dependent on the local structure of substrates. In some cases, the gauche steric interaction developed in the transition state was considered to be responsible for the observed diastereoselectivity. The present method enables an efficient synthesis of a variety of alpha,alpha'-substituted seven- to nine-membered cyclic ethers from readily accessible lactone precursors.

    DOI: 10.1021/jo4025545

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  • Total Synthesis and Structure Revision of Didemnaketal B 査読

    Haruhiko Fuwa, Takashi Muto, Kumiko Sekine, Makoto Sasaki

    CHEMISTRY-A EUROPEAN JOURNAL   20 ( 7 )   1848 - 1860   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Didemnaketal B, a structurally complex spiroacetal that exhibits potent HIV-1 protease inhibitory activity, was originally discovered by Faulkner and his colleagues from the ascidian Didemnum sp. collected at Palau. Its absolute configuration was proposed on the basis of degradation/derivatization experiments of the authentic sample. However, our total synthesis of the proposed structure of didemnaketal B questioned the stereochemical assignment made by Faulkner et al. Here we describe in detail our first total synthesis of the proposed structure 2 of didemnaketal B, which features 1) a convergent synthesis of the C7-C21 spiroacetal domain by means of a strategy exploiting Suzuki-Miyaura coupling, 2) an Evans syn-aldol reaction and a vinylogous Mukaiyama aldol reaction for the assembly of the C1-C7 acyclic domain, and 3) a Nozaki-Hiyama-Kishi reaction for the construction of the C21-C28 side chain domain. The NMR spectroscopic discrepancies observed between synthetic 2 and the authentic sample as well as careful inspection of the Faulkner's stereochemical assignment led us to postulate that the absolute configuration of the C10-C20 domain of 2 has been erroneously assigned. Accordingly, the total synthesis of the revised structure 65 was achieved to show that the NMR spectroscopic properties of synthetic 65 were in good agreement with those of the authentic sample. Furthermore, application of the phenylglycine methyl ester ( PGME) method to the C7-C21 spiroacetal domain enabled us to establish the absolute configuration of didemnaketal B.

    DOI: 10.1002/chem.201303713

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  • Studies toward the total synthesis of iriomoteolide-2a

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products   2013年10月

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    記述言語:英語   出版者・発行元:新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」  

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  • Synthesis and Biological Evaluation of Aspergillide A/Neopeltolide Chimeras 査読

    Haruhiko Fuwa, Kenkichi Noto, Masato Kawakami, Makoto Sasaki

    CHEMISTRY LETTERS   42 ( 9 )   1020 - 1022   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHEMICAL SOC JAPAN  

    In this study, stereoisomeric aspergillide A/neopeltolide chimeras were synthesized in a parallel manner, and their antiproliferative activity was evaluated to demonstrate the potential utility of the 14-membered macrolactone structure embedded with a tetrahydropyran substructure as a template for developing natural product-like antiproliferative agents.

    DOI: 10.1246/cl.130322

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  • Total synthesis and biological evaluation of marine macrolide natural products

    H. Fuwa

    Abstracts of the 70th Anniversary Symposium of the Chemical Society of Japan Tohoku Branch   94   2013年9月

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    記述言語:英語   出版者・発行元:日本化学会東北支部  

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  • Total Synthesis of the Proposed Structure of Didemnaketal B 査読

    Haruhiko Fuwa, Kumiko Sekine, Makoto Sasaki

    ORGANIC LETTERS   15 ( 15 )   3970 - 3973   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Total synthesis of the proposed structure of didemnaketal B has been accomplished. The C7-C21 spiroacetal domain was synthesized by exploiting our Suzuki-Miyaura coupling/spiroacetalization strategy. The C1-C7 acyclic domain was constructed via an Evans syn-aldol reaction and a vinylogous Mukaiyama aldol reaction. Finally, the C22-C28 side chain was introduced by means of a Nozaki-Hiyama-Kishi reaction. Comparison of the NMR spectroscopic data of our synthetic material with those of the authentic sample revealed that the proposed structure requires stereochemical reassignment.

    DOI: 10.1021/ol4017518

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  • Concise synthesis and biological assessment of (+)-neopeltolide and a 16-member stereoisomer library of 8,9-dehydroneopeltolide: Identification of pharmacophoric elements 査読

    Haruhiko Fuwa, Masato Kawakami, Kenkichi Noto, Takashi Muto, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki

    Chemistry - A European Journal   19 ( 25 )   8100 - 8110   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    We describe herein a concise synthesis of (+)-neopeltolide, a marine macrolide natural product that elicits a highly potent antiproliferative activity against several human cancer cell lines. Our synthesis exploited the powerful bond-forming ability and high functional group compatibility of olefin metathesis and esterification reactions to minimize manipulations of oxygen functionalities and to maximize synthetic convergency. Our findings include a chemoselective olefin cross-metathesis reaction directed by H-bonding, and a ring-closing metathesis conducted under non-high dilution conditions. Moreover, we developed a 16-member stereoisomer library of 8,9-dehydroneopeltolide to systematically explore the stereostructure-activity relationships. Assessment of the antiproliferative activity of the stereoisomers against A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma, HT-1080 human fibrosarcoma, and P388 murine leukemia cell lines has revealed marked differences in potency between the stereoisomers. This study provides comprehensive insights into the structure-activity relationship of this important antiproliferative agent, leading to the identification of the pharmacophoric structural elements and the development of truncated analogues with nanomolar potency. SAR of (+)-neopeltolide: A modular synthetic route to (+)-neopeltolide, a potent antiproliferative marine macrolide, was established by exploiting the esterification/olefin metathesis strategy, and a 16-member stereoisomer library of 8,9-dehydeoneopeltolide was developed to elucidate the stereostructure- activity relationships (see figure). Copyright © 2013 WILEY-VCH Verlag GmbH &amp
    Co. KGaA, Weinheim.

    DOI: 10.1002/chem.201300664

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  • Total synthesis and biological evaluation of (+)-gambieric acid A and its analogues 査読

    K. Ishigai

    Chemistry - A European Journal   19 ( 17 )   5276 - 5288   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

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  • Total Synthesis of 13-Demethyllyngbyaloside B 査読

    Haruhiko Fuwa, Naoya Yamagata, Asami Saito, Makoto Sasaki

    ORGANIC LETTERS   15 ( 7 )   1630 - 1633   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Total synthesis of 13-demethyllyngbyaloside B, an unnatural analogue of a marine macrolide glycoside lyngbyaloside B, has been achieved. The 14-membered macrocyclic backbone was constructed in a convergent manner via esterification and ring-closing metathesis. The bromodiene side chain was introduced by means of a Stille-type reaction and a subsequent bromodesilylation. Finally, the rhamnopyranose unit was stereoselectively introduced by glycosylation under Schmidt conditions.

    DOI: 10.1021/ol400408w

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  • Total synthesis and biological evaluation of (–)-exiguolide analogues: Importance of the macrocyclic backbone 査読

    H. Fuwa, ほか

    Organic & Biomolecular Chemistry   11 ( 21 )   3442 - 3450   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry  

    DOI: 10.1039/c3ob40131f

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  • A concise synthesis of the AB-ring fragment of (–)-gambierol 査読

    H. Fuwa, K. Hirota, M. Sasaki

    Heterocycles   86 ( 1 )   127 - 132   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本複素環化学研究所  

    DOI: 10.3987/COM-12-S(N)21

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  • Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization: concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives 査読

    Haruhiko Fuwa, Takuma Noguchi, Kenkichi Noto, Makoto Sasaki

    ORGANIC & BIOMOLECULAR CHEMISTRY   10 ( 40 )   8108 - 8112   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    Herein, we describe the concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives based on a domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization (CM/IOCC) reaction. We have found that the domino CM/IOCC of delta-hydroxy olefins with alpha,beta-unsaturated carbonyl compounds (e.g., trans-crotonaldehyde or N-acryloyl-2,5-dimethylpyrrole) could be efficiently achieved in the presence of the second-generation Hoveyda-Grubbs catalyst under elevated temperature conditions, directly affording 2,6-cis-substituted tetrahydropyrans in excellent yields with synthetically useful diastereoselectivity ("auto-tandem catalysis"). In addition, we have found that the domino CM/IOCC of delta-hydroxy olefins with alpha,beta-unsaturated carbonyl compounds could be achieved simply by performing CM in the presence of a Bronsted acid in CH2Cl2 at 25-35 degrees C, which delivered 2,6-cis-substituted tetrahydropyrans in good yields with excellent diastereoselectivity ("orthogonal-tandem catalysis"). To understand the mechanism of auto-tandem catalysis in the domino CM/IOCC reaction, we have investigated the role of ruthenium hydride complexes in the IOCC of a zeta-hydroxy alpha,beta-unsaturated ketone as a model case.

    DOI: 10.1039/c2ob26189h

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  • Total synthesis and structure-activity relationships of marine macrolide natural products

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products   2012年10月

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    記述言語:英語   出版者・発行元:新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」  

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  • P-60 ガンビエロールの構造単純化類縁体の合成と生物活性評価(ポスター発表の部)

    菅 悠人, 不破 春彦, 後藤 智見, 今野 悠, 佐々木 誠, Alonso Eva, Vale Carmen, Botana Luis Miguel

    天然有機化合物討論会講演要旨集   ( 54 )   633 - 638   2012年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Gambierol (1), a polycyclic ether natural neurotoxin isolated from the ciguatera causative dinoflagellate, Gambierdiscus toxicus has been reported to be a potent and subtype-selective blocker of voltage-gated potassium channels (VGPCs). Previous studies of marine polycyclic ether molecules have suggested the importance of the whole skeleton of polycyclic ether for potent biological activity. We have previously investigated the peripheral structure-activity relationships of Gambierol, however, it remained unclear whether the full length of polycyclic ether skeleton is essential for its toxicity. In this presentation, we designed and synthesized two structurally simplified analogues of Gambierol comprising BCDEFGH- and EFGH- rings of the parent compound (2 and 3). Surprisingly, both analogues showed comparable potency to Gambierol on VGPCs inhibition in cerebellar granule cells of mice. These results indicated that we obtained the easily synthesized analogues of Gambierol that have potent biological activity. Moreover, to investigate the additional functions of truncated analogues, we examined the effect of these compounds in a model of Alzheimer's disease (AD) obtained from triple transgenic mice, which expresses amyloid beta (An) accumulation and tau hyperphosphorylation. In vitro preincubation of the neurons of these mice with Gambierol or analogues decreased steady-state level of the NMDA receptor subunit 2A without affecting the 2B subunit. In addition, treatment of these compounds reduced the intra- and extracellular levels of Aβ and the levels of hyperphosphorylated tau. This study constitutes the first discovery of designed structurally simplified analogues of polycyclic ether compound possessing potent biological activity. Furthermore, it suggested the practicality of gambierol and analogues as chemical probes for understanding the function of VGPCs and the mechanism of modulation of the accumulation of Aβ and hyperphosphorylated tau by NMDA receptors.

    DOI: 10.24496/tennenyuki.54.0_633

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  • 32 ガンビエル酸Aの全合成と完全立体構造決定(口頭発表の部)

    不破 春彦, 石貝 和也, 橋詰 佳祐, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 54 )   187 - 192   2012年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Gambieric acid A (1) is a marine polycyclic ether natural product that was isolated from the ciguatera causative dinoflagellate Gambierdiscus toxicus. Despite its structural similarity to ciguatoxins and brevetoxins, 1 only weakly binds to voltage-gated sodium channels and does not exhibit lethal toxicity against mice at 1 mg/kg (ip). Instead, 1 displays extraordinary potent antifungal activity against Aspergillus niger. Our previous studies on the synthesis and NMR analysis of suitably designed model compounds have strongly suggested that the stereochemical assignment of the originally proposed structure of 1 is questionable and led us to propose that the absolute configuration of the polycyclic ether domain of 1 is opposite to that of the natural product. Here, we disclose the first total synthesis and complete stereostructure of 1. The B-ring was first synthesized based on our methodology for the synthesis of medium-sized cyclic ethers. The A-ring was next forged via stereoselective bromoetherification. Suzuki-Miyaura coupling of the A/B-ring exo-olefin with an acetate-derived enol phosphate followed by ring-closing metathesis (RCM) constructed the D-ring, and mixed-thioacetalization and one-pot oxidation/methylation methodologies were used to close the C-ring. The A/BCD- and F'GHIJ-ring fragments were coupled by means of Suzuki-Miyaura coupling. After establishment of the C25 stereogenic center by exploiting the conformational bias of the F'-ring, oxidative cleavage of the F'-ring followed by elaboration of the E-ring via stereoselective allylation of a mixed thioacetal by using glycosylation chemistry, and ensuing closure of the F-ring furnished the entire polycyclic ether backbone. Finally, the J-ring side chain was introduced by means of modified Julia-Kocienski olefination to complete the first total synthesis of gambieric acid A (1). The spectroscopic data, optical rotation value, and antifungal activity of synthetic 1 matched those of the natural product. Thus, our total synthesis confirmed the correctness of our revised structure and unambiguously established the complete stereostructure of 1.

    DOI: 10.24496/tennenyuki.54.0_187

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  • Effect of gambierol and its heptacyclic and tetracyclic analogues in cultured cerebellar neurons: A structure–activity relationships study 査読

    S. Pérez

    Chemical Research in Toxicology   25 ( 9 )   1929 - 1937   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/tx300242m

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  • Stereoselective synthesis of the C1–C16 fragment of goniodomin A 査読

    M. Nakajima, H. Fuwa, M. Sasaki

    Bulletin of the Chemical Society of Japan   85 ( 9 )   948 - 956   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本化学会  

    DOI: 10.1246/bcsj.20120152

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  • Total Synthesis and Complete Stereostructure of Gambieric Acid A 査読

    Haruhiko Fuwa, Kazuya Ishigai, Keisuke Hashizume, Makoto Sasaki

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   134 ( 29 )   11984 - 11987   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Total synthesis of gambieric acid A, a potent antifungal polycyclic ether metabolite, has been accomplished for the first time, which firmly established the complete stereostructure of this natural product.

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  • TOTAL SYNTHESIS OF TETRAHYDROPYRAN-CONTAINING NATURAL PRODUCTS EXPLOITING INTRAMOLECULAR OXA-CONJUGATE CYCLIZATION 査読

    Haruhiko Fuwa

    HETEROCYCLES   85 ( 6 )   1255 - 1298   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A growing number of tetrahydropyran-containing biologically active substances are being discovered from nature. Intramolecular oxa-conjugate cyclization (IOCC) is known as one of the most powerful methodologies for the stereoselective synthesis of substituted tetrahydropyran derivatives, although there is clearly room for methodological improvement. In this review, we describe our successful total synthesis of tetrahydropyran-containing natural products by exploiting IOCC and the discoveries that we have made during the course of the synthetic campaigns.

    DOI: 10.3987/REV-12-730

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  • 海洋天然物のケミカルバイオロジー:ブリオスタチンとイグジグオリドへの合成化学的アプローチ

    不破春彦

    化学と生物   50 ( 6 )   404 - 405   2012年6月

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    記述言語:日本語   出版者・発行元:日本農芸化学会  

    DOI: 10.1271/kagakutoseibutsu.50.404

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  • Design and synthesis of skeletal analogues of gambierol: Attenuation of amyloid β and tau pathology with voltage-gated potassium channel and N-methyl-D-aspartate receptor implications 査読

    E. Alonso

    Journal of the American Chemical Society   134 ( 17 )   7467 - 7479   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ja300565t

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  • Stereoselective synthesis of 2,6-cis-substituted tetrahydropyrans: Brønsted acid-catalyzed intramolecular oxa-conjugate cyclization of α,β-unsaturated ester surrogates 査読

    H. Fuwa, N. Ichinokawa, K. Noto, M. Sasaki

    The Journal of Organic Chemistry   77 ( 6 )   2588 - 2607   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/jo202179s

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  • Total synthesis of (–)-brevenal: A streamlined strategy for practical synthesis of polycyclic ethers 査読

    M. Ebine, H. Fuwa, M. Sasaki

    Chemistry - A European Journal   17 ( 49 )   13754 - 13761   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/chem.201101437

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  • Recent applications of the Suzuki–Miyaura cross-coupling to complex polycyclic ether synthesis 査読

    H. Fuwa, M. Ebine, M. Sasaki

    有機合成化学協会誌   69 ( 11 )   1251 - 1262   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:有機合成化学協会  

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  • Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of a fully elaborated GHIJ-ring fragment 査読

    Koichi Tsubone, Keisuke Hashizume, Haruhiko Fuwa, Makoto Sasaki

    TETRAHEDRON   67 ( 35 )   6600 - 6615   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A stereocontrolled synthesis of a fully elaborated GHIJ-ring fragment of gambieric acids, which are potent antifungal polycyclic ether natural products, has been accomplished. The synthesis features convergent assembly of the tetracyclic polyether skeleton through aldol coupling/cyclodehydration/reductive etherification processes and stereoselective construction of the J-ring side chain by a CeCl(3)-promoted Julia-Kocienski olefination. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2011.05.082

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  • A new strategy for the synthesis of substituted dihydropyrones and tetrahydropyrones via palladium-catalyzed coupling of thioesters 査読

    Haruhiko Fuwa, Kana Mizunuma, Seiji Matsukida, Makoto Sasaki

    TETRAHEDRON   67 ( 27-28 )   4995 - 5010   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In this paper, we describe a new strategy for the synthesis of substituted dihydropyrones and tetrahydropyrones. By exploiting palladium-catalyzed coupling of thioesters with terminal alkynes or alkenylboronic acids, a variety of beta-hydroxy ynones or enones, respectively, could be prepared in an efficient manner under mild conditions. AgOTf-promoted intramolecular oxa-conjugate cyclization of beta-hydroxy ynones provided 2,6-substituted dihydropyrones in excellent yields. On the other hand, acid-catalyzed cyclization of beta-hydroxy enones caused racemization of the product 2,6-substituted tetrahydropyrones due to its reversible nature. Eventually, stereoselective hydrogenation of substituted dihydropyrones was found to be a solid and efficient approach for the synthesis of 2,6-cis-substituted tetrahydropyrone derivatives. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2011.03.114

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  • Comparative Cytotoxicity of Gambierol versus Other Marine Neurotoxins 査読

    E. Cagide, M. C. Louzao, B. Espina, I. R. Ares, M. R. Vieytes, M. Sasaki, H. Fuwa, C. Tsukano, Y. Konno, M. Yotsu-Yamashita, L. A. Paquette, T. Yasumoto, L. M. Botana

    CHEMICAL RESEARCH IN TOXICOLOGY   24 ( 6 )   835 - 842   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Many microalgae produce compounds that exhibit potent biological activities. Ingestion of marine organisms contaminated with those toxins results in seafood poisonings. In many cases, the lack of toxic material turns out to be an obstacle to make the toxicological investigations needed. In this study, we evaluate the cytotoxicity of several marine toxins on neuroblastoma cells, focusing on gambierol and its effect on cytosolic calcium levels. In addition, we compared the effects of this toxin with ciguatoxin, brevetoxin, and gymnocin-A, with which gambierol shares a similar ladder-like backbone, as well as with polycavernoside A analogue 5, a glycosidic macrolide toxin. For this purpose, different fluorescent dyes were used: Fura-2 to monitor variations in cytosolic calcium levels, Alamar Blue to detect cytotoxicity, and Oregon Green 514 Phalloidin to quantify and visualize modifications in the actin cytoskeleton. Data showed that, while gambierol and ciguatoxin were successful in producing a calcium influx in neuroblastoma cells, gymnocin-A was unable to modify this parameter. Nevertheless, none of the toxins induced morphological changes or alterations in the actin assembly. Although polycavernoside A analogue 5 evoked a sharp reduction of the cellular metabolism of neuroblastoma cells, gambierol scarcely reduced it, and ciguatoxin, brevetoxin, and gymnocin-A failed to produce any signs of cytotoxicity. According to this, sharing a similar polycyclic ether backbone is not enough to produce the same effects on neuroblastoma cells; therefore, more studies should be carried out with these toxins, whose effects may be being underestimated.

    DOI: 10.1021/tx200038j

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  • Biosynthesis-inspired intramolecular oxa-conjugate cyclization of α,β-unsaturated thioesters: Stereoselective synthesis of 2,6-cis-substituted tetrahydropyrans 査読

    H. Fuwa, K. Noto, M. Sasaki

    Organic Letters   13 ( 7 )   1820 - 1823   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol200333p

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  • A convergent synthesis of the C1–C16 segment of goniodomin A via palladium-catalyzed organostannane–thioester coupling 査読

    H. Fuwa, ほか

    Organic Letters   13 ( 5 )   1106 - 1109   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol1031409

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  • Total synthesis and biological assessment of (–)-exiguolide and analogues

    H. Fuwa

    日本化学会第91春季年会要旨集(Asian International Symposium)   2011年3月

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    記述言語:英語   出版者・発行元:日本化学会  

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  • Total synthesis and biological assessment of (–)-exiguolide and analogues 査読

    H. Fuwa, ほか

    Chemistry - A European Journal   17 ( 9 )   2678 - 2688   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/chem.201003135

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  • Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling 査読

    Masahiro Sonoshita, Masahiro Aoki, Haruhiko Fuwa, Koji Aoki, Hisahiro Hosogi, Yoshiharu Sakai, Hiroki Hashida, Arimichi Takabayashi, Makoto Sasaki, Sylvie Robine, Kazuyuki Itoh, Kiyoko Yoshioka, Fumihiko Kakizaki, Takanori Kitamura, Masanobu Oshima, Makoto Mark Taketo

    CANCER CELL   19 ( 1 )   125 - 137   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on insoluble nuclear matrix. In tumor cells, Notch signaling was triggered by ligands on adjoining blood vessels, and stimulated transendothelial migration. Genetic depletion of Aes in Apc(Delta 716) intestinal polyposis mice caused marked tumor invasion and intravasation that were suppressed by Notch signaling inhibition. These results suggest that inhibition of Notch signaling can be a promising strategy for prevention and treatment of colon cancer metastasis.

    DOI: 10.1016/j.ccr.2010.11.008

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  • Palladium-Catalyzed Synthesis of N- and O-Heterocycles Starting from Enol Phosphates 査読

    Haruhiko Fuwa

    SYNLETT   ( 1 )   6 - 29   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:GEORG THIEME VERLAG KG  

    In this Account, we describe our efforts in the development of new synthetic strategies for the construction of N- and O-heterocycles by exploiting palladium-catalyzed reactions using enol phosphates as an electrophilic component.

    DOI: 10.1055/s-0030-1259104

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  • Synthetic studies on goniodomin A: Convergent assembly of the C15–C36 segment via palladium-catalyzed organostannane–thioester coupling 査読

    T. Saito, H. Fuwa, M. Sasaki

    Tetrahedron   67 ( 2 )   429 - 445   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.tet.2010.11.017

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  • Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain 査読

    Koichi Tsubone, Keisuke Hashizume, Haruhiko Fuwa, Makoto Sasaki

    TETRAHEDRON LETTERS   52 ( 4 )   548 - 551   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A stereocontrolled synthesis of the GHIJ-ring fragment having a side chain of gambieric acids, which are potent antifungal polycyclic ether natural products, has been achieved. The synthesis features convergent assembly of the tetracyclic polyether skeleton by using aldol coupling and stereoselective construction of the J-ring side chain by a cerium chloride-promoted Julia-Kocienski reaction. (C) 2010 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2010.11.127

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  • Total Synthesis of Structurally Complex Marine Oxacyclic Natural Products 査読

    Haruhiko Fuwa

    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN   83 ( 12 )   1401 - 1420   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHEMICAL SOC JAPAN  

    Total synthesis of structurally complex marine oxacyclic natural products, (-)-gambierol, (-)-brevenal, and (+)-neopeltolide, has been accomplished by exploiting Suzuki-Miyaura coupling of enol phosphates, paving the way for biological investigations on these scarcely available substances.

    DOI: 10.1246/bcsj.20100209

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  • Convergent Assembly of the Spiroacetal Subunit of Didemnaketal B 査読

    Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki

    ORGANIC LETTERS   12 ( 22 )   5354 - 5357   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A highly convergent synthesis of the C9-C28 spiroacetal subunit of didemnaketal B has been accomplished. Assembly of the C9-C15 alkylborate and C16-C21 enol phosphate by means of Suzuki-Miyaura coupling and acid-catalyzed cyclization of the derived dihydroxy enol ether enabled a rapid and efficient construction of the spiroacetal subunit. The C22-C28 side chain was incorporated via Nozaki-Hiyama-Kishi coupling to complete the synthesis.

    DOI: 10.1021/ol1024713

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  • The marine polyether gambierol enhances muscle contraction and blocks a transient K+ current in skeletal muscle cells 査読

    Sebastien Schlumberger, Gilles Ouanounou, Emmanuelle Girard, Makoto Sasaki, Haruhiko Fuwa, M. Carmen Louzao, Luis M. Botana, Evelyne Benoit, Jordi Molgo

    TOXICON   56 ( 5 )   785 - 791   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Gambierol is a complex marine toxin first isolated with ciguatoxins from cell cultures of the toxic dinoflagellate Gambierdiscus toxicus. Despite the chemical complexity of the polycyclic ether toxin, the total successful synthesis of gambierol has been achieved by different chemical strategies. In the present work the effects of synthetic gambierol on mouse and frog skeletal neuromuscular preparations and Xenopus skeletal myocytes have been studied. Gambierol (0.1-5 mu M) significantly increased isometric twitch tension in neuromuscular preparations stimulated through the motor nerve. Less twitch augmentation was observed in directly stimulated muscles when comparing twitch tension-time integrals obtained by nerve stimulation. Also, gambierol induced small spontaneous muscle contraction originating from presynaptic activity that was completely inhibited by D-tubocurarine. Gambierol slowed the rate of muscle action potential repolarization, triggered spontaneous and/or repetitive action potentials, and neither affected action potential amplitude nor overshoot in skeletal muscle fibers. These results suggest that gambierol through an action on voltage-gated K+ channels prolongs the duration of action potentials, enhances the extent and time course of Ca2+ release from the sarcoplasmic reticulum, and increases twitch tension generation. Further evidence is provided that gambierol at sub-micromolar concentrations blocks a fast inactivating outward K+ current that is responsible for action potential prolongation in Xeno pus skeletal myocytes. (C) 2010 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.toxicon.2010.06.001

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  • 31 (-)-Exiguolideの全合成(口頭発表の部)

    不破 春彦, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 52 )   181 - 186   2010年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    (-)-Exiguolide was isolated from the sponge Geodia exigua collected off Amami-Oshima, Japn, by Ohta, Ikegami, and co-workers. The gross structure including the relative stereochemistry was established through extensive 2D NMR studies, conformational analysis on the basis of ^3J_<H,H> values and NOE correlations, and JBCA method. The molecular structure, characterized by the 20-membered macrolactone core embedded with a methylene bis(tetrahydropyran) substructure, is related to that of bryostains. (-)-Exiguolide inhibits fertilization of the sea urchin gametes but not embryogenesis of the fertilized egg. These structural and biological aspects led to an assumption that (-)-exiguolide may represent a simplified analogue of the bryostatins by Nature and render this natural product an intriguing target for organic chemists. Herein, we present the enantioselective total synthesis of (-)-exiguolide, the nturally occurring enantiomer, for the first time. The methylene bis(tetrahydropyran) substructure was efficiently constructed in a convergent fashion. Thus, the readily available C1-C7 and C8-C16 segments were assembled through olefin cross-metathesis, and two tetrahydreopyran rings were successively forged via intramolecular oxa-conjugate cyclization and reductive etherification. Stereoselective formation of the sterically encumbered C16-C17 double bond was achieved via Julia-Kocienski olefination. The 20-membered macrolactone framework was constructed in an excellent yield by means of Yamaguchi macrolactonization. An alternative approach toward the macrocycle based on ring-closing metathesis was less effecient than the macrolactonization approach. Finally, the (E,Z,E)-triene side chain was introduced in a stereoselective manner via Suzuki-Miyaura coupling under exceptionally mild conditions.

    DOI: 10.24496/tennenyuki.52.0_181

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  • An enantioselective total synthesis of aspergillides A and B 査読

    Haruhiko Fuwa, Hiroshi Yamaguchi, Makoto Sasaki

    TETRAHEDRON   66 ( 38 )   7492 - 7503   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    An enantioselective total synthesis of aspergillides A and B has been accomplished on the basis of a unified synthetic strategy that exploits stereodivergent intramolecular oxa-conjugate cyclization and Yamaguchi macrolactonization. (C) 2010 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2010.07.062

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  • Studies toward the Total Synthesis of Gambieric Acids: Stereocontrolled Synthesis of a DEFG-Ring Model Compound 査読

    Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki

    JOURNAL OF ORGANIC CHEMISTRY   75 ( 15 )   5072 - 5082   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A stereocontrolled convergent synthesis of a DEFG-ring model compound of gambieric acids, highly potent antifungal marine polycyclic ether natural products, has been achieved based on Suzuki-Miyaura coupling. Conformational analysis of the model compound revealed that the nine-membered F-ring exists exclusively as a single stable conformer, as opposed to that of ciguatoxins.

    DOI: 10.1021/jo1008146

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  • A concise total synthesis of (±)-centrolobine 査読

    H. Fuwa, K. Noto, M. Sasaki

    Heterocycles   82 ( 1 )   641 - 647   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本複素環化学研究所  

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  • An efficient synthesis of 2,6-disubstituted 2,3-dihydro-4H-pyran-4-ones 査読

    H. Fuwa, S. Matsukida, M. Sasaki

    Synlett   1239 ( 1242 )   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1055/s-0029-1219794

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  • Calcium Oscillations Induced by Gambierol in Cerebellar Granule Cells 査読

    E. Alonso, C. Vale, M. Sasaki, H. Fuwa, Y. Konno, S. Perez, M. R. Vieytes, L. M. Botana

    JOURNAL OF CELLULAR BIOCHEMISTRY   110 ( 2 )   497 - 508   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Gambierol is a marine polyether ladder toxin derived from the dinoflagellate Gambierdiscus toxicus. To date, gambierol has been reported to act either as a partial agonist or as an antagonist of sodium channels or as a blocker of voltage-dependent potassium channels. In this work, we examined the cellular effect of gambierol on cytosolic calcium concentration, membrane potential and sodium and potassium membrane currents in primary cultures of cerebellar granule cells. We found that at concentrations ranging from 0.1 to 30 mu M, gambierol-evoked [Ca(2+)]c oscillations that were dependent on the presence of extracellular calcium, irreversible and highly synchronous. Gambierol-evoked [Ca(2+)]c oscillations were completely eliminated by the NMDA receptor antagonist APV and by riluzole and delayed by CNQX. In addition, the K(+) channel blocker 4-aminopyridine (4-AP)-evoked cytosolic calcium oscillations in this neuronal system that were blocked by APV and delayed in the presence of CNQX. Electrophysiological recordings indicated that gambierol caused membrane potential oscillations, decreased inward sodium current amplitude and decreased also outward IA and IK current amplitude. The results presented here point to a common mechanism of action for gambierol and 4-AP and indicate that gambierol-induced oscillations in cerebellar neurons are most likely secondary to a blocking action of the toxin on voltage-dependent potassium channels and hyperpolarization of sodium current activation. J. Cell. Biochem. 110: 497-508, 2010. (C) 2010 Wiley-Liss, Inc.

    DOI: 10.1002/jcb.22566

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  • An Efficient Synthesis of 2,6-Disubstituted 2,3-Dihydro-4H-pyran-4-ones via Sonogashira Coupling of p-Toluenethiol Esters 査読

    Haruhiko Fuwa, Seiji Matsukida, Makoto Sasaki

    SYNLETT   ( 8 )   1239 - 1242   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:GEORG THIEME VERLAG KG  

    An efficient strategy for the synthesis of 2,6-disubstituted 2,3-dihydro-4H-pyran-4-ones has been developed, which relied on Sonogashira coupling of alkynes and p-toluenethiol esters and AgOTf-promoted 6-endo-dig cyclization of the derived beta-hydroxy ynones.

    DOI: 10.1055/s-0029-1219794

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  • A Unified Total Synthesis of Aspergillides A and B 査読

    Haruhiko Fuwa, Hiroshi Yamaguchi, Makoto Sasaki

    ORGANIC LETTERS   12 ( 8 )   1848 - 1851   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    An enantioselective total synthesis of aspergillides A and B has been accomplished based on a unified strategy, wherein a hydroxy-directed, highly chemoselective olefin cross-metathesis and a diastereoselective intramolecular oxa-conjugate cyclization were employed to forge the 2,6-substituted tetrahydropyran substructure.

    DOI: 10.1021/ol100463a

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  • Stereoselective Synthesis of Substituted Tetrahydropyrans via Domino Olefin Cross-Metathesis/Intramolecular Oxa-Conjugate Cyclization 査読

    Haruhiko Fuwa, Kenkichi Noto, Makoto Sasaki

    ORGANIC LETTERS   12 ( 7 )   1636 - 1639   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A novel strategy for the stereoselective synthesis of substituted tetra hydropyrans has been developed on the basis of a domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization catalyzed by the Hoveyda-Grubbs second-generation catalyst.

    DOI: 10.1021/ol100431m

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  • Total synthesis of (–)-exiguolide 査読

    H. Fuwa, M. Sasaki

    Organic Letters   12 ( 3 )   584 - 587   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol902778y

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  • Highly efficient synthesis of medium-sized lactones via oxidative lactonization: concise total synthesis of isolaurepan 査読

    Makoto Ebine, Yuto Suga, Haruhiko Fuwa, Makoto Sasaki

    ORGANIC & BIOMOLECULAR CHEMISTRY   8 ( 1 )   39 - 42   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    A catalytic amount of TEMPO in the presence of PhI(OAc)(2) effected oxidative lactonization of 1,6- and 1,7-diols, directly affording seven- and eight-membered lactones, respectively, in good yields.

    DOI: 10.1039/b919673k

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  • A Concise Total Synthesis of (+)-Neopeltolide

    Haruhiko Fuwa, Asami Saito, Makoto Sasaki

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   49 ( 17 )   3041 - 3044   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1002/anie.201000624

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  • A Concise Total Synthesis of (+)-Neopeltolide 査読

    Haruhiko Fuwa, Asami Saito, Makoto Sasaki

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   49 ( 17 )   3041 - 3044   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1002/anie.201000624

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  • Toward the total synthesis of goniodomin A, an actin-targeting marine polyether macrolide: Convergent synthesis of the C15–C36 segment 査読

    T. Saito, H. Fuwa, M. Sasaki

    Organic Letters   11 ( 22 )   5274 - 5277   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol902217q

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  • P-41 ガンビエル酸Aの全合成研究(ポスター発表の部)

    不破 春彦, 石貝 和也, 野地 紗也加, 局 興一, 橋詰 佳祐, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 51 )   359 - 364   2009年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Gambieric acids (GAs) are marine polycyclic ether natural products, isolated from the ciguatera causative dinoflagellate Gambierdiscus toxicus by Nagai, Yasumoto, and co-workers. The molecular architecture of GAs is composed of a nonacyclic polyether core and a side chain including a tetrahydrofuran. GAs show minimal toxocity against mammalians but display extraordinary potent antifungal activity against Aspergillus niger. The highly complicated structures coupled with the interesting biological activity make GAs attractive synthetic targets. We have previously reported the synthesis of the B-J-ring polycyclic ether core of gambieric acid A (GAA). Herein we report our efforts toward the total synthesis of GAA, which culminated in the stereochemical reassignment of the nonacyclic polyether core and the synthesis of the A/B-, DEFG-, and GHJI-ring fragments. The synthesis and NMR analysis of the A/BC-ring fragment of gambieric acid B confirmed that the absolute configuration of the polycyclic ether core of GAs is opposite to that of the originally proposed structure. Accordingly, we synthesized the A/B-ring fragment of GAA wigh the correct stereochemistry, wherein the A-ring was constructed via a Suzuki-Miyaura coupling and a diastereoselective iodoetherification. We devised a new strategy for the stereocontrolled synthesis of the DEFG-ring fragment of GAs, wherein a Suzuki-Miyaura coupling was implemented as the fragment assembly process and a seven-membered cyclic ether was utilized as a template for controlling the C25 stereogenic center. We also completed the synthesis of the GHIJ-ring fragment of GAs in a convergent manner. The G- and J-rings were assembled through an aldol coupling and the H- and I-rings were constructed by cyclodehydration and reductive etherification, respectively.

    DOI: 10.24496/tennenyuki.51.0_359

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  • Stereocontrolled Synthesis of the DEFG-ring Skeleton of Gambieric Acids 査読

    Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki

    CHEMISTRY LETTERS   38 ( 8 )   866 - 867   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHEMICAL SOC JAPAN  

    A stereocontrolled entry to the DEFG-ring skeleton of gambieric acids, potent antifungal polycyclic ether natural products, has been developed based on the Suzuki-Miyaura coupling as the fragment assembly process and the use of an oxepane as a template for controlling the C25 stereogenic center.

    DOI: 10.1246/cl.2009.866

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  • Proteomic Analysis Reveals Multiple Patterns of Response in Cells Exposed to a Toxin Mixture 査読

    Gian Luca Sala, Giuseppe Ronzitti, Makoto Sasaki, Haruhiko Fuwa, Takeshi Yasumoto, Albertino Bigiani, Gian Paolo Rossini

    CHEMICAL RESEARCH IN TOXICOLOGY   22 ( 6 )   1077 - 1085   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We have used proteomic analyses to probe the responses induced by a pair of marine biotoxins, okadaic acid (OA) and gambierol (GB), added alone or in combination to a cultured cell line and carried out a preliminary investigation into the possible interactions between toxins possessing two different molecular mechanisms of action at a cellular level. When MCF-7 cells were treated with OA, we found that cellular levels of 30 proteins were significantly affected, including several isoforms of nonphosphorylated and phosphorylated hsp 27, as well as enzymes involved in the maintenance of nucleoside triphosphate pools and the control of redox states of the cell. When we repeated our analysis using GB, nine proteins were significantly affected, including some isoforms of nonphosphorylated hsp 27, as well as semenogelin-1, myosin-7, and the ATP synthase subunit delta. The combined addition of OA and GB to MCF-7 cells, in turn, affected 14 proteins, including some isoforms of nonphosphorylated and phosphorylated hsp 27, as well as myosin-7, the ATP synthase subunit delta, and enzymes involved in the control of redox states of the cell. If components affected by either OA or GB, as well as by the combined treatment, were classified according to the detected changes, two sets of data were obtained, including the components whose levels were found affected by the combined treatment, regardless of the effect observed after addition of only one agent, and those that had been found affected in cells that had been challenged with only one toxin but not when cells had been subjected to the combined treatment. Multiple patterns of responses to the toxin mixture were recorded in the two sets, consisting of both independent and interacting actions, among which we detected synergistic, similar, and antagonistic effects.

    DOI: 10.1021/tx900044p

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  • Synthetic Studies on Gambieric Acids, Potent Antifungal Polycyclic Ether Natural Products: Reassignment of the Absolute Configuration of the Nonacyclic Polyether Core by NMR Analysis of Model Compounds 査読

    Haruhiko Fuwa, Kazuya Ishigai, Tomomi Goto, Akihiro Suzuki, Makoto Sasaki

    JOURNAL OF ORGANIC CHEMISTRY   74 ( 11 )   4024 - 4040   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A highly stereocontrolled, convergent synthesis of the A/B-ring fragment of gambieric acids (GAs) has been developed on the basis of (i) a Suzuki-Miyaura coupling of the C1-C6 alkylborate and the C7-C17 vinyl iodide and (ii) a diastereoselective haloetherification for the construction of the A-ring tetrahydrofuran as key steps. Inspection of the (1)H and (13)C NMR chemical shifts of the synthesized A/B-ring model compounds led to a stereochemical reassignment of the absolute configuration of the polycyclic ether core of GAS. This structure revision was further supported by a synthesis of the A/BC-ring model compound of gambieric acid B and a comparison of its (1)H and (13)C NMR data with those of the natural product.

    DOI: 10.1021/jo900332q

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  • 抗腫瘍性マクロリド (+)-ネオペルトリドの全合成 査読

    佐々木誠, 不破春彦

    ファルマシア   45 ( 5 )   439 - 443   2009年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本薬学会  

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  • Synthesis of 2-substituted indoles and indolines via Suzuki–Miyaura coupling/5-endo-trig cyclization strategies 査読

    H. Fuwa, M. Sasaki

    The Journal of Organic Chemistry   74 ( 1 )   212 - 221   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/jo801985a

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  • Total Synthesis and Biological Evaluation of (+)-Neopeltolide and Its Analogues 査読

    Haruhiko Fuwa, Asami Saito, Shinya Naito, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki

    CHEMISTRY-A EUROPEAN JOURNAL   15 ( 46 )   12807 - 12818   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    The stereocontrolled total synthesis of the originally proposed (1) and correct (2) structures of (+)-neopeltolide, a novel marine macrolide natural product with highly potent anti-proliferative activity against several cancer cell lines as well as potent antifungal activity, has been achieved by exploiting a newly developed Suzuki-Miyaura coupling/ring-closing metathesis strategy. Alkylborate 44, which was generated in situ from iodide 34, was coupled with enol phosphate 8 by a Suzuki-Miyaura coupling. Ring-closing metathesis of the derived diene 45 followed by stereoselective hydrogenation afforded tetrahydropyran 47 as a single stereoisomer in high overall yield from 34. Our convergent strategy enabled us to construct the 14-membered macrolactone core structure of 2 in a rapid and efficient manner. Total synthesis and biological evaluation of synthetic intermediates and designed synthetic analogues, performed to establish the structure-activity relationships of 2, led to the discovery of a structurally simple yet potent cytotoxic analogue, 9-demethylneopeltolide (54).

    DOI: 10.1002/chem.200901675

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  • P-34 ブレベナールの第二世代全合成(ポスター発表の部)

    海老根 真琴, 不破 春彦, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 50 )   641 - 646   2008年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Brevenal is a pentacyclic polyether natural product isolated from the red tide dinoflagellate Karenia brevis. This natural product competitively displaces tritiated dihydrobrevetoxin-B ([^3H]-PbTx3) from voltage-sensitive sodium channels in a dose dependent manner, whereas it showed no toxicity in a fish bioassay. Moreover, brevenal increased tracheal mucus velocity in picomolar concentrations in an animal model of asthma. Thus, brevenal represents a potential lead for the development of novel therapeutic agents for treatment of mucociliary dysfunction associated with cystic fibrosis and other lung disorders. Toward elucidation of the biological mode of action at the molecular level and establishment of the structure-activity relationships, it is essential to develop an efficient, scalable, and flexible synthetic route to brevenal; however, our first-generation total synthesis involved lengthy fragment syntheses and tedious and capricious manipulations unsuitable for scale-up. Herein, we describe a highly convergent and efficient synthesis of the pentacyclic polyether core 2, which is a key intermediate in the previous synthesis. The present synthesis features i) highly efficient and scalable synthesis of the AB- and DE-ring fragments and ii) two-fold use of our Suzuki-Miyaura coupling/mixed thioacetalization-based convergent strategy for the synthesis of polycyclic ether frameworks. Our second-generation synthesis (total number of steps: 59; longest linear sequence: 32) is considerably more efficient than the original one (total number of steps: 73; longest linear sequence: 50).

    DOI: 10.24496/tennenyuki.50.0_641

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  • P-72 鈴木-宮浦カップリング反応を基盤とする天然物全合成(ポスター発表の部)

    不破 春彦, 内藤 真也, 後藤 智見, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 50 )   755 - 760   2008年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    In modern organic synthesis, the Suzuki-Miyaura coupling has been extensively utilized in the synthesis of structurally complex natural products and pharmaceuticals due to the powerful C-C bond forming ability, mild reaction conditions, and compatibility with virtually all functional groups. Although aryl and alkenyl halides and their triflate counterparts are generally used as an electrophilic component in the Suzuki-Miyaura coupling, α-heteroatom substituted alkenyl halides and triflates, potentially useful precursors for the synthesis of heterocycles, are difficult to prepare and handle because of their inherent instability. During the course of our synthetic studies on marine polycyclic ether natural products, we found that lactone-derived enol phosphates are stable enough for isolation/purification and are sufficiently reactive under the Suzuki-Miyaura conditions to yield cross-coupled products in high yields. Our continuous efforts to broaden the scope of the alkenyl phosphate-based palladium chemistry have culminated in the development of several efficient methods for the synthesis of heterocycles such as dihydropyrans and indoles. Here we report the total synthesis of cytotoxic marine metabolites, attenols A and B and (+)-neopeltolide, exploiting our recently developed strategy for the synthesis of dihydropyrans based on a sequential Suzuki-Miyaura coupling/ring-closing metathesis.

    DOI: 10.24496/tennenyuki.50.0_755

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  • A New Method for the Generation of Indole-2,3-quinodimethanes from Allenamides 査読

    Haruhiko Fuwa, Tomomi Tako, Makoto Ebine, Makoto Sasaki

    CHEMISTRY LETTERS   37 ( 9 )   904 - 905   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHEMICAL SOC JAPAN  

    A new method for the generation of indole-2,3-quinodi-methanes based on a palladium-catalyzed cascade process starting from N-(o-iodophenyl)allenamides has been developed.

    DOI: 10.1246/cl.2008.904

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  • TOTAL SYNTHESIS OF ISOINDOLOBENZAZEPINE ALKALOIDS, LENNOXAMINE AND CHILENINE, BASED ON PALLADIUM-CATALYZED REDUCTION OF ALKENYL PHOSPHATES 査読

    Haruhiko Fuwa, Makoto Sasaki

    HETEROCYCLES   76 ( 1 )   521 - 539   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    An efficient method for the synthesis of enol ethers and enecarbamates has been developed based on palladium(0)-catalyzed chemoselective reduction of alkenyl phosphates. This method has been applied successfully to the total synthesis of two isoindolobenzazepine alkaloids, lennoxamine and chilenine.

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  • An efficient strategy for the synthesis of endocyclic enol ethers and its application to the synthesis of spiroacetals 査読

    Haruhiko Fuwa, Makoto Sasaki

    ORGANIC LETTERS   10 ( 12 )   2549 - 2552   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    An efficient strategy for the synthesis of endocyclic enol ethers based on a Suzuki-Miyaura coupling/ring-closing metathesis sequence has been developed. The strategy has successfully been applied to the synthesis of spiroacetals, including cytotoxic marine metabolites attenols A and B.

    DOI: 10.1021/ol800815t

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  • Total synthesis of (–)-brevenal: A concise synthetic entry to the pentacyclic polyether core 査読

    M. Ebine, H. Fuwa, M. Sasaki

    Organic Letters   10 ( 11 )   2275 - 2278   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol800685c

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  • Stereocontrolled synthesis of the A/B-ring fragment of gambieric acid B: Reassignment of the absolute configuration of the polycyclic ether region 査読

    Haruhiko Fuwa, Tomomi Goto, Makoto Sasaki

    ORGANIC LETTERS   10 ( 11 )   2211 - 2214   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Stereocontrolled synthesis of the A/B-ring fragment of the originally assigned structure of gambieric acid B and its possible diastereomers has been accomplished. Detailed comparison of their (1)H and (13)C NMR data with those of the corresponding moiety of the natural product culminated in a stereochemical reassignment of the absolute configuration of the polycyclic ether region of gambieric acid B.

    DOI: 10.1021/ol800642t

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  • Convergent strategies for the total synthesis of polycyclic ether marine metabolites 査読

    Makoto Sasaki, Haruhiko Fuwa

    NATURAL PRODUCT REPORTS   25 ( 2 )   401 - 426   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    Marine polycyclic ether natural products continue to fascinate chemists and biologists due to their exceptionally large and complex molecular architectures and potent and diverse biological activities. Tremendous progress has been made over the past decade toward the total synthesis of marine polycyclic ether natural products. In this area, a convergent strategy for assembling small fragments into an entire molecule always plays a key role in successful total synthesis. This review describes our efforts to develop convergent strategies for the synthesis of polycyclic ethers and their application to the total synthesis of gambierol, gymnocin-A, and brevenal, and to the partial synthesis of the central part of ciguatoxins and the nonacyclic polyether skeleton of gambieric acids.

    DOI: 10.1039/b705664h

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  • Total synthesis of (+)-neopeltolide 査読

    Haruhiko Fuwa, Shinya Naito, Tomomi Goto, Makoto Sasaki

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   47 ( 25 )   4737 - 4739   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    DOI: 10.1002/anie.200801399

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  • Recent advances in the synthesis of marine polycyclic ether natural products 査読

    Haruhiko Fuwa, Makoto Sasaki

    CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT   10 ( 6 )   784 - 806   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:THOMSON SCIENTIFIC  

    For more than twenty years, chemists and biologists have been fascinated by the highly complex molecular architectures and the diverse and potent biological activities of marine polycyclic ether natural products. Given the scarce availability of these intriguing substances from natural sources, total chemical synthesis is the only way to obtain sufficient quantities for biological investigation. This review describes recent synthetic advances in the field of marine polycyclic ether natural products and their successful implementation in total synthesis endeavors.

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  • Strategies for the synthesis of 2-substituted indoles and indolines starting from acyclic α-phosphoryloxy enecarbamates 査読

    H. Fuwa, M. Sasaki

    Organic Letters   9 ( 17 )   3347 - 3350   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ol071312a

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  • Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-secretase inhibitors 査読

    H. Fuwa

    ACS Chemical Biology   2 ( 6 )   408 - 418   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/cb700073y

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  • Stereoselective synthesis of the AB-ring fragment of gambieric acid A 査読

    Haruhiko Fuwa, Akihiro Suzuki, Kazushi Sato, Makoto Sasaki

    HETEROCYCLES   72 ( 1 )   139 - 144   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Stereoselective synthesis of the AB-ring fragment of gambieric acid A has been accomplished, wherein (i) an acetylide-aldehyde coupling for fragment assembly and (ii) construction of the tetrahydrofuran A-ring via a diastereoselective bromoetherification were successfully employed as key transformations.

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  • An efficient method for the synthesis of enol ethers and enecarbamates. Total syntheses of isoindolobenzazepine alkaloids, lennoxamine and chilenine 査読

    Haruhiko Fuwa, Makoto Sasaki

    ORGANIC & BIOMOLECULAR CHEMISTRY   5 ( 12 )   1849 - 1853   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    An efficient method for the synthesis of enol ethers and enecarbamates has been developed based on catalytic hydrosilane reduction of alpha-phosphonoxy enol ethers and alpha-phosphonoxy enecarbamates. This method has been applied to the total syntheses of two isoindolobenzazepine alkaloids, lennoxamine and chilenine.

    DOI: 10.1039/b706087d

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  • A strategy for the synthesis of 2,3-disubstituted indoles starting from N-(o-halophenyl)allenamides 査読

    Haruhiko Fuwa, Makoto Sasaki

    ORGANIC & BIOMOLECULAR CHEMISTRY   5 ( 14 )   2214 - 2218   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    A strategy for the synthesis of 2,3-disubstituted indole derivatives based on an intramolecular carbopalladation-anion capture cascade has been developed, wherein construction of the pyrrole ring and functionalisation of the indole C2 and C3 positions were achieved by extensive use of palladium( 0)catalysed coupling reactions.

    DOI: 10.1039/b707338k

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  • A new method for the generation of indole-2,3-quinodimethanes and 2-(N-alkoxycarbonylamino)-1,3-dienes. Intramolecular Heck/Diels-Alder cycloaddition cascade starting from acyclic α-phosphono enecarbamates 査読

    H. Fuwa, M. Sasaki

    Chemical Communications   ( 27 )   2876 - 2878   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Royal Society of Chemistry  

    DOI: 10.1039/b704374k

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  • Concise and short synthesis of functionalized 5,6-dihydropyridin-2-ones by means of palladium(0)-catalyzed cross-coupling of ketene aminal phosphates 査読

    Haruhiko Fuwa, Akane Kaneko, Yasuaki Sugimoto, Taisuke Tomita, Takeshi Iwatsubo, Makoto Sasaki

    HETEROCYCLES   70 ( 1 )   101 - +   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A concise and short synthetic entry to 5,6-dihydropyridin-2-one derivatives has been developed by means of palladium(0)-catalyzed cross-coupling of cyclic ketene aminal phosphates.

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  • Total synthesis, structure revision, and absolute configuration of (–)-brevenal 査読

    H. Fuwa, ほか

    Journal of the American Chemical Society   128 ( 51 )   16989 - 16999   2006年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ja066772y

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  • 39 海産ポリエーテル系天然物ブレベナールの全合成と構造改訂(口頭発表の部)

    不破 春彦, 海老根 真琴, 石岡 裕貴, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 48 )   229 - 234   2006年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Brevenal is a polyether natural product isolated from laboratory cultures of the Florida red tide-forming dinoflagellate, Karenia Brevis. Its gross structure, including relative stereochemistry, was disclosed based on extensive 2D NMR studies. It has been reported that brevenal competitively displaces tritiated dihydrobrevetoxin from voltage-sensitive Na^+ channels and acts as a natural brevetoxin antagonist in vivo. More importantly, brevenal improved tracheal mucus velocity in picomolar concentrations in an animal model of asthma. Thus, it may be a source of novel therapeutic agents for treatment of cystic fibrosis and other respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). Intrigued by these biological profiles of brevenal, we embarked on the total synthesis of brevenal by means of our developed convergent methodology. Suzuki-Miyaura coupling of the AB ring enol phosphate 6 and an alkylborane derived from the DE ring exo-olefin 7 proceeded smoothly to afford coupling product 23. The C ring was then constructed by mixed-thioacetalization followed by one-pot oxidation/methylation. After construction of the left-hand (E,E)-diene side chain by means of CuTC-mediated Stille coupling, the total synthesis was completed by installing the right-hand (Z)-diene chain via Wittig reaction. However, ^1H and ^<13>C NMR spectra of synthetic 1 were not identical with those of the natural product. Detailed NMR studies suggested that the true structure of brevenal is the C26-epimer of the originally proposed structure. This notion is also supported by the postulated biosynthetic pathway of marine polyether natural products. In the event, this proved to be correct as the spectroscopic data of synthetic 2 were completely identical with those of the natural product. In addition, the optical rotation of synthetic 2 matched the value for the natural product. Thus, we succeeded in unambiguous determination of the absolute configuration of brevenal through our total synthesis endeavor.

    DOI: 10.24496/tennenyuki.48.0_229

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  • Effect of ciguatoxin 3C on voltage-gated Na+ and K+ currents in mouse taste cells 査読

    Valeria Ghiaroni, Haruhiko Fuwa, Masayuki Inoue, Makoto Sasaki, Keisuke Miyazaki, Masahiro Hirama, Takeshi Yasumoto, Gian Paolo Rossini, Giuseppe Scalera, Albertino Bigiani

    CHEMICAL SENSES   31 ( 7 )   673 - 680   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    The marine dinoflagellate Gambierdiscus toxicus produces highly lipophilic, polycyclic ether toxins that cause a seafood poisoning called ciguatera. Ciguatoxins (CTXs) and gambierol represent the two major causative agents of ciguatera intoxication, which include taste alterations (dysgeusiae). However, information on the mode of action of ciguatera toxins in taste cells is scarce. Here, we have studied the effect of synthetic CTX3C (a CTX congener) on mouse taste cells. By using the patch-clamp technique to monitor membrane ion currents, we found that CTX3C markedly affected the operation of voltage-gated Na+ channels but was ineffective on voltage-gated K+ channels. This result was the exact opposite of what we obtained earlier with gambierol, which inhibits K+ channels but not Na+ channels. Thus, CTXs and gambierol affect with high potency the operation of separate classes of voltage-gated ion channels in taste cells. Our data suggest that taste disturbances reported in ciguatera poisoning might be due to the ability of ciguatera toxins to interfere with ion channels in taste buds.

    DOI: 10.1093/chemse/bjl008

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  • Synthesis of biotinylated photoaffinity probes based on arylsulfonamide γ-secretase inhibitors 査読

    H. Fuwa, ほか

    Bioorganic & Medicinal Chemistry Letters   16 ( 16 )   4184 - 4189   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.bmcl.2006.05.091

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  • Total synthesis of the proposed structure of brevenal 査読

    Haruhiko Fuwa, Makoto Ebine, Makoto Sasaki

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   128 ( 30 )   9648 - 9650   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    DOI: 10.1021/ja062524q

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  • Synthesis of the JK/LM-ring model of prymnesins, potent hemolytic and ichthyotoxic polycyclic ethers isolated from the red tide alga Prymnesium parvum: confirmation of the relative configuration of the K/L-ring juncture 査読

    Makoto Sasaki, Naoki Takeda, Haruhiko Fuwa, Ryulchi Watanabe, Masayuki Satake, Yasukatsu Oshima

    TETRAHEDRON LETTERS   47 ( 32 )   5687 - 5691   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Synthesis of the JK/LM-ring model of prymnesins, polycyclic ether toxins isolated from the red tide phytoflagellate, Pryninesilun parvian, is described. Comparison of the H-1 and C-13 NMR data of the synthetic model with those reported for prymnesins confirmed the reported configurational assignment of the K/L-ring juncture. (c) 2006 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2006.06.032

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  • P-561 TOTAL SYNTHESIS OF THE PROPOSED STRUCTURE OF BREVENAL

    Fuwa Haruhiko, Ebine Makoto, Sasaki Makoto

    International Symposium on the Chemistry of Natural Products   2006   "P - 561"   2006年7月

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    記述言語:英語   出版者・発行元:天然有機化合物討論会  

    DOI: 10.24496/intnaturalprod.2006.0__P-561_

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  • Novel γ-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates 査読

    Y. Takahashi

    Bioorganic & Medicinal Chemistry Letters   16 ( 14 )   3813 - 3816   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.bmcl.2006.04.025

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  • Divergent synthesis of multifunctional molecular probes based on caprolactam-derived γ-secretase inhibitors and their molecular targets

    H. Fuwa, ほか

    Abstracts of 25th IUPAC International Conference on Biodiversity and Natural Products   2006年7月

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    記述言語:英語   出版者・発行元:International Union of Pure and Applied Chemistry  

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  • Carboxyl-terminal fragment of Presenilin is the molecular target of a dipeptidic γ-secretase-specific inhibitor DAPT 査読

    Y. Morohashi, ほ

    The Journal of Biological Chemistry   281 ( 21 )   14670 - 14676   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The American Society for Biochemistry and Molecular Biology  

    DOI: 10.1074/jbc.M513012200

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  • The sodium channel of human excitable cells is a target for gambierol 査読

    M. Carmen Louzao, Eva Cagide, Mercedes R. Vieytes, Makoto Sasaki, Haruhiko Fuwa, Takeshi Yasumoto, Luis M. Botana

    CELLULAR PHYSIOLOGY AND BIOCHEMISTRY   17 ( 5-6 )   257 - 268   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background: Gambierol is a polycyclic ether toxin with the same biogenetic origin as ciguatoxins. Gambierol has been associated with neurological symptoms in humans even though its mechanism of action has not been fully characterized. Methods: We studied the effect of gambierol in human neuroblastoma cells by using bis-oxonol to measure membrane potential and FURA-2 to monitor intracellular calcium. Results: We found that this toxin: i) produced a membrane depolarization, ii) potentiated the effect of veratridine on membrane potential iii) decreased ciguatoxin-induced depolarization and iv) increased cytosolic calcium in neuroblastoma cells. Conclusion: These results indicate that gambierol modulate ion fluxes by acting as a partial agonist of sodium channels. Copyright (c) 2006 S. Karger AG, Basel.

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  • Synthesis and biological evaluation of gambierol analogues: Efforts toward the development of biotinylated photoaffinity labeling probes

    H. Fuwa, ほか

    Abstracts of PACIFICHEM2005   2005年12月

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    記述言語:英語   出版者・発行元:PACIFICHEM2005  

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  • Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells 査読

    Ghiaroni, V, M Sasaki, H Fuwa, GP Rossini, G Scalera, T Yasumoto, P Pietra, A Bigiani

    TOXICOLOGICAL SCIENCES   85 ( 1 )   657 - 665   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Ciguatera is a food poisoning caused by toxins of Gambierdiscus toxicus, a marine dinoflagellate. The neurological features of this intoxication include sensory abnormalities, such as paraesthesia, heightened nociperception, and also taste alterations. Here, we have evaluated the effect of gambierol, one of the possible ciguatera toxins, on the voltage-gated ion currents in taste cells. Taste cells are excitable cells endowed with voltage-gated Na+, K+, and Cl- currents (I-Na, I-K, and I-Cl, respectively). By applying the patch-clamp technique to single cells in isolated taste buds obtained from the mouse vallate papilla, we have recorded such currents and determined the effect of bath-applied gambierol. We found that this toxin markedly inhibited I-K in the nanomolar range (IC50 of 1.8 nM), whereas it showed no significant effect on I-Na or I-Cl even at high concentration (1 mu M). The block of I-K was irreversible even after a 50-min wash. In addition to affecting the current amplitude, we found that gambierol significantly altered both the activation and inactivation processes of I-K. In conclusion, unlike other toxins involved in ciguatera, such as ciguatoxins, which affect the functioning of voltage-gated sodium channels, the preferred molecular target of gambierol is the voltage-gated potassium channel, at least in taste cells. Voltage-gated potassium currents play an important role in the generation of the firing pattern during chemotransduction. Thus, gambierol may alter action potential discharge in taste cells and this could be associated with the taste alterations reported in the clinical literature.

    DOI: 10.1093/toxsci/kfi097

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  • Synthetic studies on 3-arylquinazolin-4-ones: intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-ones and its application to the synthesis of secondary aryl amines 査読

    H Fuwa, T Kobayashi, T Tokitoh, Y Torii, H Natsugari

    TETRAHEDRON   61 ( 17 )   4297 - 4312   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The general synthesis and a novel intramolecular nucleophilic aromatic substitution (SNAr) reaction of 2-carboxamido-3-arylquinazolin-4-ones, a potentially useful scaffold in the field of medicinal chemistry, are described. The synthetic utility of the SNAr reaction as a tool for the synthesis of secondary aryl amines, including diaryl amines, is also demonstrated. (c) 2005 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2005.02.038

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  • Intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-ones and its application to the synthesis of secondary aryl amines 査読

    H Fuwa, T Kobayashi, T Tokitoh, Y Torii, H Natsugari

    SYNLETT   ( 14 )   2497 - 2500   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:GEORG THIEME VERLAG KG  

    A novel intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-one derivatives induced by base treatment and its application to the expeditious synthesis of secondary aryl amines, including diaryl amines, are described.

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  • 64(P-47) 海産毒ガンビエロールの多様な構造改変体の全合成と構造活性相関(ポスター発表の部)

    不破 春彦, 夏苅 英昭, 開沼 紀子, 橘 和夫, 佐竹 真幸, 佐々木 誠

    天然有機化合物討論会講演要旨集   ( 46 )   359 - 364   2004年10月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Marine polycyclic ether class of natural products, brevetoxins and ciguatoxins being representative, has attracted a great deal of attention of chemists and biologists due to the unusually complex and gigantic molecular architecture as well as potent and diverse biological activities. Gambierol is a marine polycyclic ether isolated as a toxic constituent from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus. It is known that gambierol exerts potent toxicity against mice (MLD 50 μg/kg, ip) and the symptoms caused in mice resemble those shown by ciguatoxins, implying that gambierol is also relevant to the ciguatera seafood poisoning. Recently, Inoue et al. have disclosed that gambierol inhibits competitively the binding of brevetoxin PbTx-3 to the voltage-sensitive sodium channel in excitable membranes. However, extremely limited availability of this toxin from natural sources has prevented further detailed biological studies. We have accomplished the first total synthesis of gambierol based on our developed Suzuki-Miyaura coupling-based strategy. Herein we report the structure-activity relationships of gambierol aiming at establishment of a rational basis for the development of probe molecules useful for biochemical studies. There exist only a few precedents of structure-activity relationship studies on marine polyether natural products, probably due to the difficulties of providing ample quantities of these natural products as well as altering the structure of highly gigantic and complex molecules by chemical means. We surmised that these difficulties could be overcome by synthesizing a diverse set of analogues from a simple yet advanced intermediate of the total synthesis (diverted total synthesis). We have synthesized up to 18 structural analogues and evaluated their biological activity. MLD value against mice (ip) was used as an index. It has been shown that the presence of the C28-C29 and C32-C33 double bonds and an appropriate length of the side chain are crucial structural elements for exerting potent toxicity. The C30 axial methyl group was found to enhance the toxicity, but it is not an essential functional group. Partial reduction of the conjugated diene system within the side chain resulted in a great decrease in toxicity. On the other hand, analogues possessing isomeric conjugated diene still displayed significant activity. These suggest that the planar nature of the conjugated diene system would be an important structural feature. Interestingly, modification of the C1 or C6 hydroxyl groups has almost no influence on the toxicity. In the case of 1-deoxy and 1-O-methylgambierol, however, mice death occurred in 45-140 min (3-10 times longer than gambierol and other active analogues), suggesting the possibility that Cl hydroxyl group is relevant to the bioavailability of the molecule.

    DOI: 10.24496/tennenyuki.46.0_359

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  • Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity 査読

    H Fuwa, N Kainuma, K Tachibana, C Tsukano, M Satake, M Sasaki

    CHEMISTRY-A EUROPEAN JOURNAL   10 ( 19 )   4894 - 4909   2004年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Gambierol is a polycyclic ether toxin, which has been isolated from the marine dinoflagellate Gambierdiscus toxicus. A series of gambierol analogues have been prepared from an advanced intermediate of our total synthesis of gambierol and investigated for their toxicity against mice, thus providing the first systematic structure-activity relationships (SAR) of this polycyclic ether class of marine toxin. The SAR studies described herein clearly indicate that 1) the C28=C29 double bond within the H ring and the unsaturated side chain are the crucial structural elements required for exerting potent biological activity and 2) the C1 and C6 hydroxy groups, the C30 methyl group, and the C37=C38 double bond have little influence on the degree of neurotoxicity against mice.

    DOI: 10.1002/chem.200400355

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  • Total synthesis of polycyclic ether natural products based on Suzuki–Miyaura cross-coupling 査読

    M. Sasaki, H. Fuwa

    Synlett   ( 11 )   1851 - 1874   2004年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Georg Thieme  

    DOI: 10.1055/s-2004-830860

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  • Synthetic studies on antascomicin A: Construction of the C18–C34 fragment 査読

    H. Fuwa, Y. Okamura, H. Natsugari

    Tetrahedron   60 ( 25 )   5341 - 5352   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.tet.2004.04.072

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  • Convergent synthesis of the ABCDE ring fragment of ciguatoxins 査読

    H Fuwa, S Fujikawa, K Tachibana, H Takakura, M Sasaki

    TETRAHEDRON LETTERS   45 ( 24 )   4795 - 4799   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Synthesis of the ABCDE ring fragment of ciguatoxins has been achieved in a highly stereocontrolled and convergent manner via the B-alkyl Suzuki-Miyaura conpling-based approach. (C) 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2004.04.083

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  • Highly efficient synthesis of medium-sized lactams via intramolecular Staudinger–aza-Wittig reaction of ω-azido pentafluorophenyl ester: Synthesis and biological evaluation of LY411575 analogues 査読

    H. Fuwa, ほか

    Tetrahedron Letters   45 ( 11 )   2323 - 2326   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/j.tetlet.2004.01.087

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  • Pathological effects on mice by gambierol, possibly one of the ciguatera toxins 査読

    E Ito, F Suzuki-Toyota, K Toshimori, H Fuwa, K Tachibana, M Satake, M Sasaki

    TOXICON   42 ( 7 )   733 - 740   2003年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Gambierol was isolated from Gambierdiscus toxicus, which causes ciguatera fish poisoning. The acute toxicological effects induced in mice by synthesized gambierol were studied. The lethal doses were about 80 mug/kg by i.p. and i.v., and 150 mug/kg by p.o. The main injury by this toxin was observed in the lung, and secondary in the heart, resulting in systemic congestion. Another toxic effect was seen in the stomach, inducing hypersecretion and ulceration. With survival from the severe stage during the initial 3 h, recovery was favorable, especially after 4 days. Additional effects were not evident during 1-week post-administration observation. (C) 2003 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.toxicon.2003.09.011

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  • Synthesis and biological evaluation of gambierol analogues 査読

    H Fuwa, N Kainuma, M Satake, M Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   13 ( 15 )   2519 - 2522   2003年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Gambierol is a polycyclic ether toxin, isolated as a toxic constituent from the marine dinoflagellate Gambierdiscus toxicus. We describe here the synthesis and biological evaluation of structural analogues of gambierol. The present preliminary structure-activity relationship studies clearly indicate that the H ring functionality and the unsaturated side chain of gambierol are crucial for its potent toxicity. (C) 2003 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/S0960-894X(03)00467-0

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  • 海産ポリエーテル毒ガンビエロールの全合成

    佐々木誠, 不破春彦

    化学と生物   41 ( 5 )   283 - 285   2003年8月

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    記述言語:日本語   出版者・発行元:学会出版センター  

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  • Diazonamideの全合成:十年後に確定した分子構造

    不破春彦

    ファルマシア   39 ( 7 )   699 - 700   2003年7月

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    記述言語:日本語   出版者・発行元:日本薬学会  

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  • ガンビエロールの全合成:107段階の軌跡

    不破春彦, 佐々木誠

    化学   58 ( 5 )   32 - 37   2003年5月

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    記述言語:日本語   出版者・発行元:化学同人  

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  • Total synthesis of (–)-gambierol 査読

    H. Fuwa, N. Kainuma, K. Tachibana, M. Sasaki

    Journal of the American Chemical Society   124 ( 50 )   14983 - 14992   2002年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society  

    DOI: 10.1021/ja028167a

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  • 27 ガンビエロールの全合成(口頭発表の部)

    不破 春彦, 佐々木 誠, 橘 和夫

    天然有機化合物討論会講演要旨集   ( 44 )   157 - 162   2002年9月

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    記述言語:日本語   出版者・発行元:天然有機化合物討論会  

    Gambierol (1) is a marine polycyclic ether toxin isolated from the ciguatera causative dinoflagellate Gambierdiscus toxicus. The toxin exhibits potent toxicity against mice (LD_<50> 50μg/kg, ip), and the symptoms caused in mice resemble those shown by ciguatoxins, implying that gambierol is also responsible for ciguatera fish poisoning. However, extremely limited availability from natural sources hampered further detailed biological studies, and therefore, sample supply by practical chemical synthesis is strongly demanded. The chemical structure is characterized by the octacyclic polyether core with 18 stereogenic centers and labile triene side chain that includes conjugated (Z,Z)-diene. Herein we report the first total synthesis of gambierol, featuring convergent synthesis of the octacyclic polyether core via our B-alkyl Suzuki-Miyaura coupling strategy and stereoselective construction of the sensitive triene side chain through the Pd(PPh_3)_4/CuCl/LiCl promoted Stille coupling. The ABC ring fragment 5 was synthesized from the known olefin 7, representing the B ring. The C6 hydroxy group was installed stereoselectively by Sharpless asymmetric epoxidation of allylic alcohol 8 and subsequent reductive cleavage of the derived hydroxy epoxide. Intramolecular hetero-Michael reaction of 10 was utilized for stereoselective formation of the A ring to give 11 as a single stereoisomer. The C ring was constructed via 6-endo cyclization of vinyl epoxide 14 to afford tricyclic compound 15, which was then converted to 5 without incident. Synthesis of the EFGH ring fragment 6 started from the known ester 16. Construction of the H ring was performed by use of a SmI_2-mediated reductive cyclization methodology developed by Nakata. 6-Endo cyclization of vinyl epoxide 19 cleanly afforded the GH ring fragment 20, which was readily converted to methyl ketone 21. Reductive cyclization of 21 under Nakata conditions gave the FGH ring fragment 22, which was then transformed into the targeted fragment 6 by standard chemistry. The convergent union of the ABC and EFGH ring fragments (5 and 6, respectively) was successfully achieved by using the B-alkyl Suzuki-Miyaura coupling to yield the cross-coupled product 23 in gratifying 86% yield. Subsequent elaboration to the octacyclic polyether core 4 of gambierol was accomplished from 23 in only six steps. Compound 4 was converted to tertiary alcohol 26 in six steps via an introduction of the double bond within the H ring by Ito-Saegusa protocol. An array of careful protective group manipulations and installation of a (Z)-vinyl bromide unit led to triol 29. Cross-coupling of 29 with the known (Z)-vinyl stannane 3 under the Pd(PPh_3)_4/CuCl/LiCl promoted Stille conditions furnished gambierol 1. Spectroscopic data (^1H and ^<13>C NMR, FIRMS, CD) and mouse lethality of synthetic 1 were identical with those of authentic natural sample.

    DOI: 10.24496/tennenyuki.44.0_157

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  • Total synthesis of gambierol 査読

    H Fuwa, M Sasaki, M Satake, K Tachibana

    ORGANIC LETTERS   4 ( 17 )   2981 - 2984   2002年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    The first total synthesis of gambierol, a marine polycyclic ether toxin, has been achieved. The synthesis features the Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille coupling for the stereoselective construction of the sensitive triene side chain that includes a conjugated (Z,Z)-diene moiety.

    DOI: 10.1021/o1026394b

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  • A general strategy for the convergent synthesis of fused polycyclic ethers via B-alkyl Suzuki coupling: synthesis of the ABCD ring fragment of ciguatoxins 査読

    M Sasaki, M Ishikawa, H Fuwa, K Tachibana

    TETRAHEDRON   58 ( 10 )   1889 - 1911   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A new method for convergent coupling of fused polycyclic ethers has been developed, which relies on B-alkyl Suzuki cross-coupling of lactone-derived enol triflates or phosphates. The strategy was successfully applied to a convergent synthesis of the ABCD ring fragment 4 of ciguatoxins, the causative toxin for ciguatera fish poisoning. The synthetic route includes a convergent union of the B and D rings (18 and 29c, respectively) by the B-alkyl Suzuki coupling, introduction of a double bond into the D ring followed by reductive closure of the tetrahydropyran C ring to afford the BCD ring system 51, and, finally, ring-closing metathesis reaction to construct the oxepene A ring. (C) 2002 Elsevier Science Ltd. All rights reserved.

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  • Synthetic studies toward gambierol. Convergent synthesis of the octacyclic polyether core 査読

    H Fuwa, M Sasaki, K Tachibana

    ORGANIC LETTERS   3 ( 22 )   3549 - 3552   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    [GRAPHICS]
    A convergent synthetic route to the octacyclic polyether core of gambierol, a marine polycyclic ether toxin, has been developed, The synthesis involves construction of two fragments representing the ABC and EFGH ring systems followed by their coupling via a B-alkyl Suzuki reaction.

    DOI: 10.1021/ol0166597

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  • Synthetic studies on a marine polyether toxin, gambierol: stereoselective synthesis of the EFGH ring system via B-alkyl Suzuki coupling 査読

    H Fuwa, M Sasaki, K Tachibana

    TETRAHEDRON   57 ( 15 )   3019 - 3033   2001年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A synthetic route to the EFGH ring system (3) of gambierol (1), a marine polyether toxin isolated from the dinoflagellate Gambierdiscus toxicus, has been developed. The present synthesis features convergent coupling of the F and H rings followed by ring-closure of the G ring based on the B-alkyl Suzuki reaction of lactone-derived enol phosphates. An angular methyl group at C23 was stereoselectively introduced by treatment of sulfone 32 with trimethylaluminum. Installation of a tertiary alcohol at C21 was accomplished through stereo-selcetive dihydroxylation of exo-methylene 36 followed by selective formation of the primary p-toluensulfonate and treatment of the resultant monotosylate 40 with lithium aluminum hydride. Finally, formation of the E ring as a lactone form completed the synthesis of 3. (C) 2001 Elsevier Science Ltd. All rights reserved.

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  • Synthetic studies on a marine polyether toxin, gambierol: stereoselective synthesis of the FGH ring system via B-alkyl Suzuki coupling 査読

    H Fuwa, M Sasaki, K Tachibana

    TETRAHEDRON LETTERS   41 ( 43 )   8371 - 8375   2000年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A synthetic route to the FGH ring system of gambierol, a marine polyether toxin isolated from the dinoflagellate Gambierdiscus toxicus, has been developed. The present synthesis features B-alkyl Suzuki coupling of the F and H rings, followed by ring-closure of the G ring and stereoselective installation of 1,3-diaxial methyl groups at C21 and C23. (C) 2000 Elsevier Science Ltd. All rights reserved.

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  • Convergent synthesis of an HIJK ring model of ciguatoxin via Suzuki cross-coupling reaction 査読

    M Sasaki, K Noguchi, H Fuwa, K Tachibana

    TETRAHEDRON LETTERS   41 ( 9 )   1425 - 1428   2000年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Convergent synthesis of HIJK ring model compound 1 of ciguatoxin is described. The present synthesis relied on a palladium-catalyzed Suzuki cross-coupling reaction between eight-membered ketene acetal phosphate 2 and seven-membered alkylborane 6. (C) 2000 Elsevier Science Ltd. All rights reserved.

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  • A general method for convergent synthesis of polycyclic ethers based on Suzuki cross-coupling: Concise synthesis of the ABCD ring system of ciguatoxin 査読

    M Sasaki, H Fuwa, M Ishikawa, K Tachibana

    ORGANIC LETTERS   1 ( 7 )   1075 - 1077   1999年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    [GRAPHICS]
    A general method for convergent assembly of polyether structure has been developed based on palladium(0)-mediated Suzuki cross-coupling reaction of alkylboranes with cyclic ketene acetal phosphates. The present method allowed for coupling of medium-sited ether rings and thus a concise synthesis of the ABCD ring system of ciguatoxins has been achieved.

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  • New strategy for convergent synthesis of trans-fused polyether frameworks based on palladium-catalyzed Suzuki cross-coupling reaction 査読

    M Sasaki, H Fuwa, M Inoue, K Tachibana

    TETRAHEDRON LETTERS   39 ( 49 )   9027 - 9030   1998年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A new strategy for convergent synthesis of trans-fused polyethers based on palladium(0)-catalyzed Suzuki cross-coupling reaction of alkylboranes with cyclic enol triflates has been developed. The present method allows to construct polyether frameworks rapidly and efficiently. (C) 1998 Elsevier Science Ltd. All rights reserved.

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書籍等出版物

  • Marine Natural Products (Topics in Heterocyclic Chemistry, vol. 58)

    T. Sugai, H. Fuwa( 担当: 分担執筆 範囲: Total Synthesis of (−)-Enigmazole A)

    Springer, Singapore  2020年11月 

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    担当ページ:pp. 361-386   記述言語:英語   著書種別:学術書

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  • Total Synthesis of (−)-Enigmazole A

    T. Sugai, H. Fuwa( 担当: 分担執筆)

    Springer  2020年11月 

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    記述言語:英語   著書種別:学術書

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  • 天然有機化合物の全合成:独創的なものづくりの反応と戦略 (CSJカレントレビュー)

    不破春彦, 佐々木誠( 担当: 分担執筆 範囲: 13章 ガンビエロール構造簡略体の設計・合成・生物機能)

    化学同人  2018年3月 

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    記述言語:日本語   著書種別:学術書

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  • Strategies and Tactics in Organic Synthesis (Vol. 12)

    H. Fuwa( 担当: 分担執筆 範囲: (−)-Lyngbyaloside B, a Marine Macrolide Glycoside: Total Synthesis and Stereochemical Revision)

    Elsevier  2016年 

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    担当ページ:143-168   記述言語:英語   著書種別:学術書

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  • Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, 3rd Edition

    Luis M. Botana編( 担当: 共著 範囲: Gambierol: Synthetic aspects)

    CRC Press  2014年3月 

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    担当ページ:895-924   記述言語:英語   著書種別:学術書

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  • Toxins and Biologically Active Compounds from Marine Microalgae

    Gian Paolo Rossini編( 担当: 共著 範囲: 12章:Total synthesis of marine polycyclic ether natural products)

    CRC Press  2014年2月 

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    担当ページ:348-412   記述言語:英語   著書種別:学術書

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  • 天然物合成で活躍した反応「実験のコツとポイント」

    ( 担当: 共著 範囲: 鈴木ー宮浦カップリング)

    化学同人 有機合成化学協会編  2011年10月 

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    担当ページ:48-49   記述言語:日本語   著書種別:学術書

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MISC

  • Total Synthesis of (−)-Exiguolide, a Potent Anticancer Marine Macrolide 招待 査読

    H. Fuwa

    Heterocycles   104 ( 10 )   1709 - 1709   2022年7月

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    記述言語:英語  

    DOI: 10.3987/rev-22-983

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  • Structure determination, correction, and disproof of marine macrolide natural products by chemical synthesis 招待 査読

    H. Fuwa

    Organic Chemistry Frontiers   8   3990 - 4023   2021年7月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:RSC  

    DOI: 10.1039/D1QO00481F

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  • Synthesis-driven stereochemical assignment of marine polycyclic ether natural products 招待 査読

    H. Fuwa

    Marine Drugs   19   257   2021年4月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:MDPI  

    DOI: 10.3390/md19050257

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  • タンデム反応と複雑天然物の全合成 招待

    村田佳亮, 不破春彦

    化学工業   71   117 - 124   2020年2月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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  • 海洋マクロリド天然物iriomoteolide-2aの全合成:複雑な天然物の構造決定と生物活性評価における全合成の役割 招待 査読

    坂本渓太, 不破春彦

    有機合成化学協会誌   77 ( 8 )   831 - 840   2019年8月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:有機合成化学協会  

    DOI: 10.5059/yukigoseikyokaishi.77.831

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  • 海洋マクロリド天然物の全合成とケミカルバイオロジー (特集 ケミカルバイオロジーの新展開)

    不破 春彦

    化學工業   67 ( 9 )   668 - 675   2016年9月

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    記述言語:日本語   出版者・発行元:小峰工業出版  

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  • A strategy for the synthesis of 2,3-disubstituted indoles starting from N-(o-halophenyl)allenamides (Vol 5, pg 2214, 2007)

    Haruhiko Fuwa, Makoto Sasaki

    ORGANIC & BIOMOLECULAR CHEMISTRY   5 ( 15 )   2506 - 2506   2007年

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    記述言語:英語   出版者・発行元:ROYAL SOC CHEMISTRY  

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  • A new method for the generation of indole-2,3-quinodimethanes and 2-(N-alkoxycarbonylamino)-1,3-dienes. Intramolecular Heck/Diels-Alder cycloaddition cascade starting from acyclic alpha-phosphoryloxy enecarbamates (pg 2876, 2007)

    Haruhiko Fuwa, Makoto Sasaki

    CHEMICAL COMMUNICATIONS   ( 29 )   3106 - 3106   2007年

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    記述言語:英語   出版者・発行元:ROYAL SOC CHEMISTRY  

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  • カプロラクタム系γ-セクレターゼ阻害剤を基盤とする高機能プローブの創製

    今野悠, 不破春彦, 佐々木誠, 高橋宴子, 菅敏幸, 福山透, 夏苅英昭, 富田泰輔, 岩坪威

    日本薬学会年会要旨集   126th ( 4 )   2006年

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  • 天然物合成中間体からのγ-セクレターゼ阻害剤の探索

    小泉一二三, 高瀬真衣, 下川淳, 竹部享, 星野健太, 北陽一, 冨成祐介, 高橋宴子, 杉本康昭, 不破春彦, 富田泰輔, 横島聡, 菅敏幸, 夏苅英昭, 岩坪威, 福山透

    日本薬学会年会要旨集   126th ( 4 )   2006年

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  • 新規γ-セクレターゼ阻害剤の探索研究:ジヒドロピリドン誘導体の短段階迅速合成

    兼子茜, 不破春彦, 杉本康昭, 富田泰輔, 岩坪威, 佐々木誠

    化学系学協会東北大会プログラムおよび講演予稿集   2006   2006年

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  • Presenilin-1 is a molecular target of a dipeptidic gamma-secretase inhibitor, DAPT

    Y Morohashi, Y Tominari, N Watanabe, T Kan, H Fuwa, H Natsugari, T Fukuyama, T Tomita, T Iwatsubo

    NEUROBIOLOGY OF AGING   25   S566 - S567   2004年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE INC  

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  • Synthesis and biological evaluation of LY411575 analogues

    H. Fuwa, ほか

    Abstracts of 2nd World Congress of Pharmaceutical Society   2004年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:The International Pharmaceutical Federation  

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  • γセクレターゼ阻害剤LY411575を基盤とするプローブ分子探索研究

    不破春彦, 諸橋雄一, 岡村裕美子, 富田泰輔, 岩坪威, 菅敏幸, 福山透, 夏苅英昭

    日本薬学会年会要旨集   124th ( 2 )   2004年

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  • 海産ポリエーテル毒ガンビエロールの全合成

    不破春彦, 佐々木 誠

    有機合成化学協会誌   61 ( 8 )   742 - 751   2003年8月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(その他)   出版者・発行元:有機合成化学協会  

    The first total synthesis of gambierol, a marine polycyclic ether toxin, has been achieved. Highly efficient synthesis of the ABC and EFGH ring fragments allowed us to prepare those two advanced intermediates in multi-gram quantities. The key feature of the present total synthesis is the B-alkyl Suzuki-Miyaura coupling tactics, which culminated in the union of the advanced intermediates and convergent synthesis of the octacyclic polyether core. Introduction of the sensitive triene side chain via Pd (PPh3) 4/CuCl/LiCl-promoted Stille coupling was conducted at the final step of the synthesis.<BR>The present total synthesis supplied useful quantities of gambierol and its structural analogues for detailed biological studies : an interesting observation was gained through pathological studies. Also, preliminary structure-activity relationship studies revealed that the functionalities present in the H ring and unsaturated side chain are crucial for potent toxicity against mice.

    DOI: 10.5059/yukigoseikyokaishi.61.742

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    その他リンク: https://jlc.jst.go.jp/DN/JALC/00230309041?from=CiNii

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講演・口頭発表等

  • マクロ環化と渡環反応を基盤とするマクロリドの新合成戦略:Exiguolide の16工程全合成

    水上大地, 飯尾 慶, 小田真実, 小野寺 悠, 不破春彦

    第63回天然有機化合物討論会  2021年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 複雑な海洋天然物の全合成

    不破春彦

    有機合成化学協会関西支部有機合成夏期セミナー「明日の有機合成化学」  ( 大阪 )   2019年8月  有機合成化学協会関西支部

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • タンデム反応を基盤とした新合成法の開発 招待

    不破春彦

    第9回有機分子構築法夏の勉強会  ( 湯河原 )   2019年5月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 変異c-kit発現細胞に選択的に作用する複雑天然物の全合成と構造活性相関解析

    不破春彦

    公益財団法人旭硝子財団2018助成研究発表会  ( 東京 )   2018年7月  公益財団法人旭硝子財団

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    記述言語:日本語   会議種別:ポスター発表  

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  • Total synthesis, stereochemical revision, and biological evaluation of lyngbyaloside B, a marine macrolide glycoside 国際会議

    H. Fuwa, Y. Okuaki, N. Yamagata, M. Sasaki

    Abstracts of PACIFICHEM2015  ( ホノルル、ハワイ )   2015年12月  PACIFICHEM2015

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • 複雑天然物の全合成と構造改訂

    平成27年度化学系学協会東北大会  2015年9月 

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    記述言語:日本語  

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  • リングビアロシドBの全合成と完全立体構造決定

    不破春彦, ほか

    第57回天然有機化合物討論会  2015年9月 

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    記述言語:日本語  

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  • 海洋マクロリド天然物の全合成とケミカルバイオロジー

    日本化学会第95春季年会委員会企画「天然物化学研究の最前線」  2015年3月 

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    記述言語:日本語  

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  • Synthetic and structural studies on lyngbyaloside B, a cytotoxic marine macrolide glycoside 国際会議

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products  2014年10月  新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」

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    記述言語:英語   会議種別:ポスター発表  

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  • Studies toward the total synthesis of iriomoteolide-2a 国際会議

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products  2013年10月  新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」

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    記述言語:英語   会議種別:ポスター発表  

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  • Total synthesis and biological evaluation of marine macrolide natural products 国際会議

    H. Fuwa

    Abstracts of the 70th Anniversary Symposium of the Chemical Society of Japan Tohoku Branch  2013年9月  日本化学会東北支部

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • 海洋天然物の効率的全合成と高活性構造単純化類縁体の創出

    新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」第4回公開シンポジウム  2013年5月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • Total synthesis and structure-activity relationships of marine macrolide natural products 国際会議

    H. Fuwa

    Abstracts of International Symposium on Chemical Biology of Natural Products  2012年10月  新学術領域研究(研究領域提案型)「天然物ケミカルバイオロジー」

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • ガンビエル酸Aの全合成と完全立体構造決定

    不破春彦, 石貝和也, 橋詰佳佑, 佐々木誠

    第54回天然有機化合物討論会  2012年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 微量複雑海洋天然物の全合成とケミカルバイオロジーへの展開

    東北大学GCOEプログラム分子系高次構造体化学国際教育研究拠点シンポジウム2011  2011年11月 

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    記述言語:日本語  

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  • 海洋天然物(–)-exiguolideの全合成と生物活性評価

    日本薬学会東北支部第10回化学系薬学若手研究者セミナー/日本薬学会東北支部  2011年8月 

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    記述言語:日本語  

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  • Total synthesis and biological assessment of (–)-exiguolide and analogues 国際会議

    H. Fuwa

    日本化学会第91春季年会要旨集(Asian International Symposium)  2011年3月  日本化学会

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • Concise total synthesis of (+)-neopeltolide 国際会議

    H. Fuwa, A. Saito, M. Sasaki

    Abstracts of PACIFICHEM2010  ( ホノルル、ハワイ )   2010年12月  PACIFICHEM2010

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • (-)-Exiguolideの全合成

    不破春彦, 佐々木誠

    第52回天然有機化合物討論会  2010年10月 

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    記述言語:日本語  

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  • 複雑な構造を有する海洋天然有機化合物の効率的全合成

    日本化学会第90春季年会要旨集  2010年3月 

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    記述言語:日本語  

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  • 海産マクロリド天然物ネオペルトリドの全合成と構造活性相関

    平成21年度化学系学協会東北大会  2009年9月 

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    記述言語:日本語  

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  • スピロアセタールの効率的構築法の開発:アテノールの全合成

    不破春彦, 佐々木誠

    日本化学会第88春季年会  2008年3月 

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    記述言語:日本語  

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  • アルケニルホスフェートを出発原料とする有機分子構築法

    第42回天然物化学談話会  2007年7月 

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    記述言語:日本語  

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  • 海産ポリエーテル系天然物ブレベナールの全合成と構造改訂

    不破春彦, 海老根真琴, 石岡裕貴, 佐々木誠

    第48回天然有機化合物討論会  2006年10月 

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    記述言語:日本語  

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  • リン酸エステルを脱離基とするPd(0)触媒反応を用いる複素環合成

    第5回日本薬学会東北支部若手研究者セミナー  2006年9月 

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    記述言語:日本語  

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  • Divergent synthesis of multifunctional molecular probes based on caprolactam-derived γ-secretase inhibitors and their molecular targets 国際会議

    H. Fuwa, ほか

    Abstracts of 25th IUPAC International Conference on Biodiversity and Natural Products  ( 京都 )   2006年7月  International Union of Pure and Applied Chemistry

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    記述言語:英語   会議種別:ポスター発表  

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  • Synthesis and biological evaluation of gambierol analogues: Efforts toward the development of biotinylated photoaffinity labeling probes 国際会議

    H. Fuwa, ほか

    Abstracts of PACIFICHEM2005  ( ホノルル、ハワイ )   2005年12月  PACIFICHEM2005

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    記述言語:英語   会議種別:ポスター発表  

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  • 海産ポリエーテル系天然物の全合成研究と生命科学的展開

    第40回天然物化学談話会  2005年7月 

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    記述言語:日本語  

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  • ブレベナールの全合成研究

    不破春彦, 海老根真琴, 佐々木誠

    日本化学会第85春季年会  2005年3月 

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    記述言語:日本語  

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  • ガンビエロールの全合成

    不破春彦, 佐々木誠, 橘和夫

    第82回有機合成シンポジウム  2002年11月 

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    記述言語:日本語  

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  • ガンビエロールの全合成

    不破春彦, 佐々木誠, 橘和夫

    第44回天然有機化合物討論会  2002年10月 

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    記述言語:日本語  

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  • ガンビエロールの全合成研究

    不破春彦, 佐々木誠, 橘和夫

    日本化学会第81春季年会要旨集  2002年3月 

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    記述言語:日本語  

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  • ガンビエロールの全合成研究−EFGH環部の合成−

    不破春彦, 佐々木誠, 橘和夫

    日本化学会第79春季年会  2001年3月 

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    記述言語:日本語  

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  • 海産ポリエーテル化合物ガンビエロールの合成研究

    不破春彦, 佐々木誠, 橘和夫

    日本化学会第78春季年会  2000年3月 

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    記述言語:日本語  

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  • 鈴木クロスカップリング反応を用いる収束的ポリ環状エーテル合成法の開発とシガトキシン合成への応用

    1999年有機合成若手研究者のためのセミナー  1999年11月 

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    記述言語:日本語  

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  • 鈴木クロスカップリング反応を用いる収束的ポリエーテル骨格合成法の開発とシガトキシン合成への応用

    佐々木誠, 不破春彦, 石川誠, 橘和夫

    第75回有機合成シンポジウム  1999年6月 

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    記述言語:日本語  

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  • 収束的ポリ環状エーテル合成法の開発

    佐々木誠, 不破春彦, 井上将行, 橘和夫

    日本化学会第75秋季年会  1998年9月 

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    記述言語:日本語  

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受賞

  • 科学技術分野の文部科学大臣表彰若手科学者賞

    2011年4月   文部科学省   海洋天然有機化合物の高効率的全合成の研究

  • 日本化学会第59回進歩賞

    2010年3月   日本化学会   複雑な構造を有する海洋天然有機化合物の効率的全合成

  • 第50回天然有機化合物討論会奨励賞(ポスター発表の部)

    2008年10月   天然有機化合物討論会   鈴木-宮浦カップリング反応を基盤とする天然物全合成

  • 第4回天然物化学談話会奨励賞

    2004年7月   天然物化学談話会   海産毒ガンビエロール全合成と多様性志向型全合成による構造活性相関

  • 第44回天然有機化合物討論会奨励賞(口頭発表の部)

    2002年10月   天然有機化合物討論会   ガンビエロールの全合成

共同研究・競争的資金等の研究課題

  • 複雑海洋天然物の実践的全合成と構造改変による立体配座・活性制御

    2022年4月 - 2025年3月

    日本学術振興会  基盤研究(C) 

    不破 春彦

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    資金種別:競争的資金

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  • アンフィジニウム属渦鞭毛藻の有用二次代謝産物の探索と開発

    2021年4月 - 2025年3月

    基盤研究(B) 

    津田正史

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    資金種別:競争的資金

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  • 超活性抗腫瘍性海洋天然物の全合成研究

    2019年10月 - 2020年9月

    山田科学振興財団  研究援助 

    不破 春彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:2000000円 ( 直接経費:2000000円 )

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  • 複雑マクロリドの全合成、構造決定及び活性立体構造の解明

    2017年4月 - 2020年3月

    日本学術振興会  基盤研究(C) 

    不破 春彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • タンデム反応を基盤とする複雑海洋天然物の高効率的全合成

    2018年12月 - 2019年11月

    内藤記念科学振興財団  内藤記念科学奨励金・研究助成 

    不破 春彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:3000000円 ( 直接経費:3000000円 )

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  • 海洋産マクロリドの新合成戦略の開発と応用

    2018年4月 - 2019年3月

    東京応化科学技術振興財団  研究費の助成 

    不破 春彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1000000円 ( 直接経費:1000000円 )

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  • 複雑大環状天然物の全合成・全立体構造決定・構造活性相関解明

    2016年11月 - 2017年10月

    住友財団  基礎科学研究助成 

    不破 春彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1300000円 ( 直接経費:1300000円 )

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  • 変異c-Kit発現細胞に選択的に作用する複雑天然物の全合成と構造活性相関解析

    2015年4月 - 2017年3月

    旭硝子財団  第1分野(化学・生命科学系)研究奨励 

    不破 春彦

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    配分額:2000000円 ( 直接経費:2000000円 )

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現在の担当授業科目

  • 2023年度   卒業研究Ⅰ   学部

  • 2023年度   卒業研究Ⅱ   学部

  • 2023年度   応用化学実験2   学部

  • 2023年度   応用有機化学1   学部

  • 2023年度   有機化学1   学部

  • 2023年度   生物有機化学   学部

  • 2023年度   応用化学特殊論文研修Ⅰ   大学院

  • 2023年度   応用化学特殊論文研修Ⅱ   大学院

  • 2023年度   応用化学特殊論文研修Ⅲ   大学院

  • 2023年度   応用化学特殊論文研修Ⅳ   大学院

  • 2023年度   応用化学特殊論文研修Ⅴ   大学院

  • 2023年度   応用化学特殊論文研修Ⅵ   大学院

  • 2023年度   応用化学特論   大学院

  • 2023年度   応用化学論文研修第一   大学院

  • 2023年度   応用化学論文研修第三   大学院

  • 2023年度   応用化学論文研修第二   大学院

  • 2023年度   応用化学論文研修第四   大学院

  • 2023年度   有機合成化学特論   大学院

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委員歴

  • 2020年5月 - 現在

    Marine Drugs誌   編集委員  

  • 2022年3月 - 2024年2月

    日本化学会 関東支部   常任幹事  

  • 2019年4月 - 2021年3月

    有機合成化学協会   編集委員  

  • 2009年4月 - 2015年12月

    有機合成化学協会東北支部   常任幹事  

  • 2007年10月 - 2015年10月

    天然物化学談話会   世話人  

  • 2013年11月 -  

    Frontiers in Chemistry誌   編集委員  

▼全件表示

社会貢献活動

  • Marine Drugs誌編集委員

    役割:編集, 助言・指導, 企画

    MDPI  2020年3月 -  

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  • 有機合成化学協会誌編集委員

    役割:編集

    有機合成化学協会  2019年3月 -  

     詳細を見る