Updated on 2025/07/16
Doctor of Science ( The University of Tokyo )
Master of Science ( The University of Tokyo )
The University of Tokyo Graduate School of Science Department of Chemistry doctor course completed
The University of Tokyo Graduate School of Science Department of Chemistry master course completed
The University of Tokyo School of Science Department of Chemistry graduated
宮城県仙台第二高等学校 graduated
2017.4 -
"Professor, Faculty of Science and Engineering, Chuo University"
2009.5 - 2017.3
"Associate Professor, Graduate School of Life Sciences, Tohoku University"
2007.4 - 2009.4
"Assistant Professor, Graduate School of Life Sciences, Tohoku University"
2006.7 - 2007.3
"Research Associate, Graduate School of Life Sciences, Tohoku University"
2005.4 - 2006.6
"Postdoctoral Fellow, JSPS"
2005.2 - 2005.3
"Research Staff, Graduate School of Life Sciences, Tohoku University"
2002.10 - 2005.1
"Research Associate, Graduate School of Pharmaceutical Sciences, The University of Tokyo"
2001.4 - 2002.9
"Research Fellow, JSPS"
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
Natural product chemistry
Synthetic organic chemistry
Nanotechnology/Materials / Structural organic chemistry and physical organic chemistry / Synthetic Organic chemistry
Life Science / Bioorganic chemistry / Bioorganic chemistry
Nanotechnology/Materials / Chemistry and chemical methodology of biomolecules / Biomolecular chemistry
Life Science / Bioorganic chemistry / Synthetic Organic chemistry
Kyoya Ohyama, Taisei Masuda, Keita Sakamoto, Atsushi Yoshimura, Kyoko Tatsumoto, Keisuke Murata, Haruhiko Fuwa
The Journal of Organic Chemistry 90 2025.7
Tandem Synthesis of Pyrrolidine and Piperidine Derivatives from Propargylic Alcohols Under Multimetallic Catalysis Invited Reviewed
Tatsumi Ishii, Erika Nezu, Haruhiko Fuwa
European Journal of Organic Chemistry 28 2025.4
Reika Murakami, Tomo Mori, Keisuke Murata, Haruhiko Fuwa
The Journal of Organic Chemistry 90 753 - 767 2025.1
Tomohiro Obana, Miyu Nakajima, Kazuki Nakazato, Hayato Nakagawa, Keisuke Murata, Masashi Tsuda, Haruhiko Fuwa
Journal of the American Chemical Society 146 29836 - 29846 2024.10
Total Synthesis of (−)-Fasicularin Reviewed
Yuki Takatori, Haruhiko Fuwa
The Journal of Organic Chemistry 89 2024.7
Total Synthesis of Marine Macrolide Natural Products by the Macrocyclization/Transannular Pyran Cyclization Strategy Invited Reviewed
Haruhiko Fuwa
SYNLETT 35 1488 - 1499 2024.7
Total Synthesis of (−)-Enigmazole A by the Macrocyclization/Transannular Pyran Cyclization Strategy Reviewed
Taisei Masuda, Kyoya Ohyama, Atushi Yoshimura, Haruhiko Fuwa
Organic Letters 26 2045 - 2050 2024.3
Atomic-resolution structure analysis inside an adaptable porous framework Reviewed
Yuki Wada, Pavel M. Usov, Bun Chan, Makoto Mukaida, Ken Ohmori, Yoshio Ando, Haruhiko Fuwa, Hiroyoshi Ohtsu, Masaki Kawano
Nature Communications 15 81 2024.1
Total Synthesis of (−)-Enigmazole B Reviewed
Yoshihiro Goda, Haruhiko Fuwa
Organic Letters 25 8402 - 8407 2023.12
Hayato Nakagawa, Haruhiko Fuwa
Chemical Communications 59 10121 - 10124 2023.8
Total Synthesis of (+)-Muricatetrocin B via a Late-Stage Co-Catalyzed Hartung–Mukaiyama Cyclization Reviewed
Riko Minami, Tsubasa Kasai, Keisuke Murata, Haruhiko Fuwa
Organic Letters 25 5745 - 5749 2023.8
Collective Asymmetric Total Synthesis of Cylindricines Reviewed
Ryohei Hanzawa, Haruhiko Fuwa
Organic Letters 25 1984 - 1988 2023.3
An 11-Step Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy Reviewed
Kazuki Nakazato, Mami Oda, Haruhiko Fuwa
Bulletin of the Chemical Society of Japan 96 257 - 267 2023.2
Keisuke Murata, Hirotoshi Mori, Haruhiko Fuwa
Bulletin of the Chemical Society of Japan 95 ( 12 ) 1775 - 1785 2022.11
Stereoselective Tandem Synthesis of Pyrrolidine Derivatives under Gold Catalysis: An Asymmetric Synthesis of (−)-Lepadiformine A Reviewed
Atsushi Yoshimura, Ryohei Hanzawa, Haruhiko Fuwa
Organic Letters 24 6237 - 6241 2022.7
Total Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy Reviewed
Kazuki Nakazato, Mami Oda, Haruhiko Fuwa
Organic Letters 24 4003 - 4008 2022.6
Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells Reviewed
E. Benoit, S. Schlumberger, J. Molgó, M. Sasaki, H. Fuwa, R. Bournaud
Toxins 14 254 2022.4
Tandem Macrolactone Synthesis: Total Synthesis of (−)-Exiguolide by a Macrocyclization/Transannular Pyran Cyclization Strategy Reviewed
Daichi Mizukami, Kei Iio, Mami Oda, Yu Onodera, Haruhiko Fuwa
Angewandte Chemie, International Edition 61 e202202549 2022.3
Determination of the toxicity equivalency factors for ciguatoxins using human sodium channels Reviewed
S. Raposo-Garcia, M. C. Louzao, H. Fuwa, M. Sasaki, C. Vale, L. Botana
Food and Chemical Toxicology 160 112812 2022.1
Asymmetric Synthesis of (−)-Atorvastatin Calcium by Tandem Catalysis Reviewed
Keisuke Murata, Riko Minami, Haruhiko Fuwa
Bulletin of the Chemical Society of Japan 94 ( 8 ) 2028 - 2035 2021.9
K. Nishimura, R. Hanzawa, T. Sugai, H. Fuwa
The Journal of Organic Chemistry 86 6674 - 6697 2021.5
Stereoselective Synthesis of the Southern Hemisphere Acyclic Domain of Neaumycin B Reviewed
H. Takeshita, T. Sugai, H. Fuwa
The Journal of Organic Chemistry 86 6787 - 6799 2021.5
M. Ohta, S. Kato, T. Sugai, H. Fuwa
The Journal of Organic Chemistry 86 5584 - 5615 2021.4
Total synthesis and complete configurational assignment of amphirionin-2 Reviewed
S. Kato, D. Mizukami, T. Sugai, M. Tsuda, H. Fuwa
Chemical Science 12 ( 3 ) 872 - 879 2021.1
Unified Total Synthesis of (–)-Enigmazole A and (–)-15-O-Methylenigmazole A Reviewed
Keisuke Sakurai, Keita Sakamoto, Makoto Sasaki, Haruhiko Fuwa
Chemistry - An Asian Journal 15 3494 - 3502 2020.11
J. Molgo, S. Schulmberger, M. Sasaki, H. Fuwa, M. C. Louzao, L. M. Botana, D. Servent, E. Benoit
Neuroscience 439 106 - 116 2020.7
Tandem Three-Component Synthesis of syn-1,2- and syn-1,3-Diol Derivatives Invited Reviewed
K. Murata, H. Takeshita, K. Sakamoto, H. Fuwa
Chemistry - An Asian Journal 15 ( 6 ) 807 - 819 2020.3
Total Synthesis, Stereochemical Revision, and Biological Assessment of Iriomoteolide‐2a Reviewed International journal
K. Sakamoto, A. Hakamata, A. Iwasaki, K. Suenaga, M. Tsuda, H. Fuwa
Chemistry - A European Journal 25 ( 36 ) 8528 - 8542 2019.6
Fluorescence-labeled neopeltolide derivatives for subcellular localization imaging Reviewed International journal
S. Yanagi, T. Sugai, T. Noguchi, M. Kawakami, M. Sasaki, S. Niwa, A. Sugimoto, H. Fuwa
Organic & Biomolecular Chemistry 17 ( 28 ) 6771 - 6776 2019.6
Keisuke Murata, Keita Sakamoto, Haruhiko Fuwa
Organic Letters 21 ( 10 ) 3730 - 3734 2019.5
Ruthenium-Catalyzed Intramolecular Double Hydroalkoxylation of Internal Alkynes Reviewed
K. Iio, S. Sachimori, T. Watanabe, H. Fuwa
Organic Letters 20 7851 - 7855 2018.12
Total Synthesis of (−)‐Enigmazole A Reviewed
K. Sakurai, M. Sasaki, H. Fuwa
Angewandte Chemie, International Edition 57 ( 18 ) 5143 - 5146 2018.4
Total synthesis and stereochemical revision of iriomoteolide-2a Reviewed
K. Sakamoto, A. Hakamata, M. Tsuda, H. Fuwa
Angewandte Chemie, International Edition 57 3801 - 3805 2018.3
A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells Reviewed
Haruhiko Fuwa, Mizuho Sato
MARINE DRUGS 15 ( 10 ) 320 2017.10
Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid beta Expression in Mice Brains: Implications in AD Pathology Reviewed
Eva Alonso, Andres C. Vieira, Ines Rodriguez, Rebeca Alvarino, Sandra Gegunde, Haruhiko Fuwa, Yuto Suga, Makoto Sasaki, Amparo Alfonso, Jose Manuel Cifuentes, Luis M. Botana
ACS CHEMICAL NEUROSCIENCE 8 ( 6 ) 1358 - 1367 2017.6
(−)-Lyngbyaloside B, a Marine Macrolide Glycoside: Total Synthesis and Stereochemical Revision Reviewed
H. Fuwa
Strategies and Tactics in Organic Synthesis 12 143 - 168 2017
Exploiting ruthenium carbene-catalyzed reactions in total synthesis of marine oxacyclic natural products Reviewed
H. Fuwa, M. Sasaki
Bulletin of the Chemical Society of Japan 89 ( 12 ) 1403 - 1415 2016.12
Diastereoselective Ring-Closing Metathesis as a Means to Construct Medium-Sized Cyclic Ethers: Application to the Synthesis of a Photoactivatable Gambierol Derivative Reviewed
Yu Onodera, Kazuaki Hirota, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki, Haruhiko Fuwa
JOURNAL OF ORGANIC CHEMISTRY 81 ( 18 ) 8234 - 8252 2016.9
Effect of carbon chain length in acyl coenzyme A on the efficiency of enzymatic transformation of okadaic acid to 7-O-acyl okadaic acid Reviewed
Sachie Furumochi, Tatsuya Onoda, Yuko Cho, Haruhiko Fuwa, Makoto Sasaki, Mari Yotsu-Yamashita, Keiichi Konoki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26 ( 13 ) 2992 - 2996 2016.7
Total Synthesis and Complete Stereostructure of a Marine Macrolide Glycoside, (-)-LyngbyalosideB Reviewed
Haruhiko Fuwa, Naoya Yamagata, Yuta Okuaki, Yuya Ogata, Asami Saito, Makoto Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 22 ( 20 ) 6815 - 6829 2016.5
Complete Stereochemical Assignment of Campechic Acids A and B Reviewed
Ruri Isaka, Linkai Yu, Makoto Sasaki, Yasuhiro Igarashi, Haruhiko Fuwa
JOURNAL OF ORGANIC CHEMISTRY 81 ( 9 ) 3638 - 3647 2016.5
Toward the Total Synthesis of Amphidinolide N: Synthesis of the C8-C29 Fragment Reviewed
Yuki Kawashima, Atsushi Toyoshima, Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 18 ( 9 ) 2232 - 2235 2016.5
Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives: Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural Product Reviewed
Haruhiko Fuwa
MARINE DRUGS 14 ( 4 ) 65 2016.4
Progress toward the Total Synthesis of Goniodomin A: Stereocontrolled, Convergent Synthesis of the C12-C36 Fragment Reviewed
Haruhiko Fuwa, Seiji Matsukida, Taro Miyoshi, Yuki Kawashima, Tomoyuki Saito, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 81 ( 6 ) 2213 - 2227 2016.3
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 2015.12
Concise synthesis of the C15-C38 fragment of okadaic acid, a specific inhibitor of protein phosphatases 1 and 2A Reviewed
Haruhiko Fuwa, Keita Sakamoto, Takashi Muto, Makoto Sasaki
TETRAHEDRON 71 ( 37 ) 6369 - 6383 2015.9
Potassium currents inhibition by gambierol analogs prevents human T lymphocyte activation Reviewed
J. A. Rubiolo, C. Vale, V. Martin, H. Fuwa, M. Sasaki, L. M. Botana
ARCHIVES OF TOXICOLOGY 89 ( 7 ) 1119 - 1134 2015.7
Evaluation of gambierol and its analogs for their inhibition of human K(v)1.2 and cytotoxicity Reviewed
Keiichi Konoki, Yuto Suga, Haruhiko Fuwa, Mari Yotsu-Yamashita, Makoto Sasaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 25 ( 3 ) 514 - 518 2015.2
Concise synthesis of the C15–C38 fragment of okadaic acid: Application of Suzuki–Miyaura reaction to spiroacetal synthesis Reviewed
H. Fuwa, K. Sakamoto, T. Muto, M. Sasaki
Organic Letters 17 ( 2 ) 366 - 369 2015.2
Concise synthesis of the A/BCD-ring fragment of gambieric acid A Reviewed
Haruhiko Fuwa, Ryo Fukazawa, Makoto Sasaki
FRONTIERS IN CHEMISTRY 2 116 2015.1
Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (-)-Lyngbyaloside B Reviewed
Haruhiko Fuwa, Yuta Okuaki, Naoya Yamagata, Makoto Sasaki
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 54 ( 3 ) 868 - 873 2015.1
STUDIES TOWARD THE TOTAL SYNTHESIS OF AMPHIDINOLIDE N: STEREOCONTROLLED SYNTHESIS OF THE C13-C29 SEGMENT Reviewed
Makoto Sasaki, Yuki Kawashima, Haruhiko Fuwa
HETEROCYCLES 90 ( 1 ) 579 - 599 2015.1
Programmed Cell Death Induced by (-)-8,9-Dehydroneopeltolide in Human Promyelocytic Leukemia HL-60 Cells under Energy Stress Conditions Reviewed
Haruhiko Fuwa, Mizuho Sato, Makoto Sasaki
MARINE DRUGS 12 ( 11 ) 5576 - 5589 2014.11
Synthetic and structural studies on lyngbyaloside B, a cytotoxic marine macrolide glycoside
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2014.10
Total Synthesis and Complete Structural Assignment of Gambieric Acid A, a Large Polycyclic Ether Marine Natural Product Reviewed
Makoto Sasaki, Haruhiko Fuwa
CHEMICAL RECORD 14 ( 4 ) 678 - 703 2014.8
Synthesis and biological evaluation of (+)-neopeltolide analogues: Importance of the oxazole-containing side chain Reviewed
Haruhiko Fuwa, Takuma Noguchi, Masato Kawakami, Makoto Sasaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24 ( 11 ) 2415 - 2419 2014.6
Stereoselective Synthesis of Medium-Sized Cyclic Ethers: Application of C-Glycosylation Chemistry to Seven- to Nine-Membered Lactone-Derived Thioacetals and Their Sulfone Counterparts Reviewed
Yuto Suga, Haruhiko Fuwa, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 79 ( 4 ) 1656 - 1682 2014.2
Total Synthesis and Structure Revision of Didemnaketal B Reviewed
Haruhiko Fuwa, Takashi Muto, Kumiko Sekine, Makoto Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 20 ( 7 ) 1848 - 1860 2014.2
Studies toward the total synthesis of iriomoteolide-2a
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2013.10
Synthesis and Biological Evaluation of Aspergillide A/Neopeltolide Chimeras Reviewed
Haruhiko Fuwa, Kenkichi Noto, Masato Kawakami, Makoto Sasaki
CHEMISTRY LETTERS 42 ( 9 ) 1020 - 1022 2013.9
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 2013.9
Total Synthesis of the Proposed Structure of Didemnaketal B Reviewed
Haruhiko Fuwa, Kumiko Sekine, Makoto Sasaki
ORGANIC LETTERS 15 ( 15 ) 3970 - 3973 2013.8
Concise synthesis and biological assessment of (+)-neopeltolide and a 16-member stereoisomer library of 8,9-dehydroneopeltolide: Identification of pharmacophoric elements Reviewed
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 2013.6
Total synthesis and biological evaluation of (+)-gambieric acid A and its analogues Reviewed
K. Ishigai
Chemistry - A European Journal 19 ( 17 ) 5276 - 5288 2013.5
Total Synthesis of 13-Demethyllyngbyaloside B Reviewed
Haruhiko Fuwa, Naoya Yamagata, Asami Saito, Makoto Sasaki
ORGANIC LETTERS 15 ( 7 ) 1630 - 1633 2013.4
Total synthesis and biological evaluation of (-)-exiguolide analogues: importance of the macrocyclic backbone Reviewed
Haruhiko Fuwa, Kana Mizunuma, Makoto Sasaki, Takaya Suzuki, Hiroshi Kubo
ORGANIC & BIOMOLECULAR CHEMISTRY 11 ( 21 ) 3442 - 3450 2013
A CONCISE SYNTHESIS OF THE AB-RING FRAGMENT OF (-)-GAMBIEROL Reviewed
Haruhiko Fuwa, Kazuaki Hirota, Makoto Sasaki
HETEROCYCLES 86 ( 1 ) 127 - 132 2012.12
Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization: concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives Reviewed
Haruhiko Fuwa, Takuma Noguchi, Kenkichi Noto, Makoto Sasaki
ORGANIC & BIOMOLECULAR CHEMISTRY 10 ( 40 ) 8108 - 8112 2012.10
Total synthesis and structure-activity relationships of marine macrolide natural products
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2012.10
P-60 Synthesis and Biological Evaluation of Structurally Simplified Analogues of Gambierol(Poster Presentation)
Suga Yuto, Fuwa Haruhiko, Goto Tomomi, Konno Yu, Sasaki Makoto, Alonso Eva, Vale Carmen, Botana Luis Miguel
Symposium on the Chemistry of Natural Products, symposium papers ( 54 ) 633 - 638 2012.9
32 Total Synthesis and Complete Stereostructure of Gambieric Acid A(Oral Presentation)
Fuwa Haruhiko, Ishigai Kazuya, Hashizume Keisuke, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 54 ) 187 - 192 2012.9
Effect of Gambierol and Its Tetracyclic and Heptacyclic Analogues in Cultured Cerebellar Neurons: A Structure-Activity Relationships Study Reviewed
Sheila Perez, Carmen Vale, Eva Alonso, Haruhiko Fuwa, Makoto Sasaki, Yu Konno, Tomomi Goto, Yuto Suga, Mercedes R. Vieytes, Luis M. Botana
CHEMICAL RESEARCH IN TOXICOLOGY 25 ( 9 ) 1929 - 1937 2012.9
Stereoselective Synthesis of the C1-C16 Fragment of Goniodomin A Reviewed
Motohiro Nakajima, Haruhiko Fuwa, Makoto Sasaki
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 85 ( 9 ) 948 - 956 2012.9
Total Synthesis and Complete Stereostructure of Gambieric Acid A Reviewed
Haruhiko Fuwa, Kazuya Ishigai, Keisuke Hashizume, Makoto Sasaki
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 ( 29 ) 11984 - 11987 2012.7
TOTAL SYNTHESIS OF TETRAHYDROPYRAN-CONTAINING NATURAL PRODUCTS EXPLOITING INTRAMOLECULAR OXA-CONJUGATE CYCLIZATION Reviewed
Haruhiko Fuwa
HETEROCYCLES 85 ( 6 ) 1255 - 1298 2012.6
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 2012.6
Design and Synthesis of Skeletal Analogues of Gambierol: Attenuation of Amyloid-beta and Tau Pathology with Voltage-Gated Potassium Channel and N-Methyl-D-aspartate Receptor Implications Reviewed
Eva Alonso, Haruhiko Fuwa, Carmen Vale, Yuto Suga, Tomomi Goto, Yu Konno, Makoto Sasaki, Frank M. LaFerla, Mercedes R. Vieytes, Lydia Gimenez-Llort, Luis M. Botana
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 ( 17 ) 7467 - 7479 2012.5
Stereoselective Synthesis of 2,6-Cis-Substituted Tetrahydropyrans: Bronsted Acid-Catalyzed Intramolecular Oxa-Conjugate Cyclization of alpha,beta-Unsaturated Ester Surrogates Reviewed
Haruhiko Fuwa, Naoki Ichinokawa, Kenkichi Noto, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 77 ( 6 ) 2588 - 2607 2012.3
Total Synthesis of (-)-Brevenal: A Streamlined Strategy for Practical Synthesis of Polycyclic Ethers Reviewed
Makoto Ebine, Haruhiko Fuwa, Makoto Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 17 ( 49 ) 13754 - 13761 2011.12
Recent Applications of the Suzuki-Miyaura Cross-coupling to Complex Polycyclic Ether Synthesis Reviewed
Haruhiko Fuwa, Makoto Ebine, Makoto Sasaki
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 69 ( 11 ) 1251 - 1262 2011.11
Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of a fully elaborated GHIJ-ring fragment Reviewed
Koichi Tsubone, Keisuke Hashizume, Haruhiko Fuwa, Makoto Sasaki
TETRAHEDRON 67 ( 35 ) 6600 - 6615 2011.9
A new strategy for the synthesis of substituted dihydropyrones and tetrahydropyrones via palladium-catalyzed coupling of thioesters Reviewed
Haruhiko Fuwa, Kana Mizunuma, Seiji Matsukida, Makoto Sasaki
TETRAHEDRON 67 ( 27-28 ) 4995 - 5010 2011.7
Comparative Cytotoxicity of Gambierol versus Other Marine Neurotoxins Reviewed
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 2011.6
Biosynthesis-Inspired Intramolecular Oxa-Conjugate Cyclization of alpha,beta-Unsaturated Thioesters: Stereoselective Synthesis of 2,6-cis-Substituted Tetrahydropyrans Reviewed
Haruhiko Fuwa, Kenkichi Noto, Makoto Sasaki
ORGANIC LETTERS 13 ( 7 ) 1820 - 1823 2011.4
A Convergent Synthesis of the C1-C16 Segment of Goniodomin A via Palladium-Catalyzed Organostannane-Thioester Coupling Reviewed
Haruhiko Fuwa, Motohiro Nakajima, Jinglu Shi, Yoshiyuki Takeda, Tomoyuki Saito, Makoto Sasaki
ORGANIC LETTERS 13 ( 5 ) 1106 - 1109 2011.3
Total synthesis and biological assessment of (–)-exiguolide and analogues
H. Fuwa
Asian International Symposium 2011.3
Total Synthesis and Biological Assessment of (-)-Exiguolide and Analogues Reviewed
Haruhiko Fuwa, Takaya Suzuki, Hiroshi Kubo, Takao Yamori, Makoto Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 17 ( 9 ) 2678 - 2688 2011.2
Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling Reviewed
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 2011.1
Palladium-Catalyzed Synthesis of N- and O-Heterocycles Starting from Enol Phosphates Reviewed
Haruhiko Fuwa
SYNLETT ( 1 ) 6 - 29 2011.1
Synthetic studies on goniodomin A: convergent assembly of the C15-C36 segment via palladium-catalyzed organostannane-thioester coupling Reviewed
Tomoyuki Saito, Haruhiko Fuwa, Makoto Sasaki
TETRAHEDRON 67 ( 2 ) 429 - 445 2011.1
Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain Reviewed
Koichi Tsubone, Keisuke Hashizume, Haruhiko Fuwa, Makoto Sasaki
TETRAHEDRON LETTERS 52 ( 4 ) 548 - 551 2011.1
Total Synthesis of Structurally Complex Marine Oxacyclic Natural Products Reviewed
Haruhiko Fuwa
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 83 ( 12 ) 1401 - 1420 2010.12
Convergent Assembly of the Spiroacetal Subunit of Didemnaketal B Reviewed
Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki
ORGANIC LETTERS 12 ( 22 ) 5354 - 5357 2010.11
The marine polyether gambierol enhances muscle contraction and blocks a transient K+ current in skeletal muscle cells Reviewed
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 2010.10
Total Synthesis of (-)-Exiguolide
Fuwa Haruhiko, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 52 ) 181 - 186 2010.9
An enantioselective total synthesis of aspergillides A and B Reviewed
Haruhiko Fuwa, Hiroshi Yamaguchi, Makoto Sasaki
TETRAHEDRON 66 ( 38 ) 7492 - 7503 2010.9
Studies toward the Total Synthesis of Gambieric Acids: Stereocontrolled Synthesis of a DEFG-Ring Model Compound Reviewed
Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 75 ( 15 ) 5072 - 5082 2010.8
A concise total synthesis of (±)-centrolobine Reviewed
H. Fuwa, K. Noto, M. Sasaki
Heterocycles 82 ( 1 ) 641 - 647 2010.6
An efficient synthesis of 2,6-disubstituted 2,3-dihydro-4H-pyran-4-ones Reviewed
H. Fuwa, S. Matsukida, M. Sasaki
Synlett 1239 ( 1242 ) 2010.5
Calcium Oscillations Induced by Gambierol in Cerebellar Granule Cells Reviewed
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 2010.5
An Efficient Synthesis of 2,6-Disubstituted 2,3-Dihydro-4H-pyran-4-ones via Sonogashira Coupling of p-Toluenethiol Esters Reviewed
Haruhiko Fuwa, Seiji Matsukida, Makoto Sasaki
SYNLETT ( 8 ) 1239 - 1242 2010.5
A Unified Total Synthesis of Aspergillides A and B Reviewed
Haruhiko Fuwa, Hiroshi Yamaguchi, Makoto Sasaki
ORGANIC LETTERS 12 ( 8 ) 1848 - 1851 2010.4
Stereoselective Synthesis of Substituted Tetrahydropyrans via Domino Olefin Cross-Metathesis/Intramolecular Oxa-Conjugate Cyclization Reviewed
Haruhiko Fuwa, Kenkichi Noto, Makoto Sasaki
ORGANIC LETTERS 12 ( 7 ) 1636 - 1639 2010.4
Total Synthesis of (-)-Exiguolide Reviewed
Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 12 ( 3 ) 584 - 587 2010.2
Highly efficient synthesis of medium-sized lactones via oxidative lactonization: concise total synthesis of isolaurepan Reviewed
Makoto Ebine, Yuto Suga, Haruhiko Fuwa, Makoto Sasaki
ORGANIC & BIOMOLECULAR CHEMISTRY 8 ( 1 ) 39 - 42 2010
A Concise Total Synthesis of (+)-Neopeltolide
Haruhiko Fuwa, Asami Saito, Makoto Sasaki
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 49 ( 17 ) 3041 - 3044 2010
A Concise Total Synthesis of (+)-Neopeltolide Reviewed
Haruhiko Fuwa, Asami Saito, Makoto Sasaki
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 49 ( 17 ) 3041 - 3044 2010
Toward the Total Synthesis of Goniodomin A, An Actin-Targeting Marine Polyether Macrolide: Convergent Synthesis of the C15-C36 Segment Reviewed
Tomoyuki Saito, Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 11 ( 22 ) 5274 - 5277 2009.11
Studies toward the Total Synthesis of Gambieric Acid A
Fuwa Haruhiko, Ishigai Kazuya, Noji Sayaka, Tsubone Koichi, Hashizume Keisuke, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 51 ) 359 - 364 2009.9
Stereocontrolled Synthesis of the DEFG-ring Skeleton of Gambieric Acids Reviewed
Haruhiko Fuwa, Sayaka Noji, Makoto Sasaki
CHEMISTRY LETTERS 38 ( 8 ) 866 - 867 2009.8
Proteomic Analysis Reveals Multiple Patterns of Response in Cells Exposed to a Toxin Mixture Reviewed
Gian Luca Sala, Giuseppe Ronzitti, Makoto Sasaki, Haruhiko Fuwa, Takeshi Yasumoto, Albertino Bigiani, Gian Paolo Rossini
CHEMICAL RESEARCH IN TOXICOLOGY 22 ( 6 ) 1077 - 1085 2009.6
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 Reviewed
Haruhiko Fuwa, Kazuya Ishigai, Tomomi Goto, Akihiro Suzuki, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 74 ( 11 ) 4024 - 4040 2009.6
抗腫瘍性マクロリド (+)-ネオペルトリドの全合成 Reviewed
佐々木誠, 不破春彦
ファルマシア 45 ( 5 ) 439 - 443 2009.5
Synthesis of 2-Substituted Indoles and Indolines via Suzuki-Miyaura Coupling/5-endo-trig Cyclization Strategies Reviewed
Haruhiko Fuwa, Makoto Sasaki
JOURNAL OF ORGANIC CHEMISTRY 74 ( 1 ) 212 - 221 2009.1
Total Synthesis and Biological Evaluation of (+)-Neopeltolide and Its Analogues Reviewed
Haruhiko Fuwa, Asami Saito, Shinya Naito, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 15 ( 46 ) 12807 - 12818 2009
P-34 Second-generation Total Synthesis of (-)-Brevenal(Poster Presentation)
EBINE Makoto, FUWA Haruhiko, SASAKI Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 50 ) 641 - 646 2008.9
P-72 Total Synthesis of Natural Products Based on Suzuki-Miyaura Coupling(Poster Presentation)
Fuwa Haruhiko, Naito Shinya, Goto Tomomi, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 50 ) 755 - 760 2008.9
A New Method for the Generation of Indole-2,3-quinodimethanes from Allenamides Reviewed
Haruhiko Fuwa, Tomomi Tako, Makoto Ebine, Makoto Sasaki
CHEMISTRY LETTERS 37 ( 9 ) 904 - 905 2008.9
TOTAL SYNTHESIS OF ISOINDOLOBENZAZEPINE ALKALOIDS, LENNOXAMINE AND CHILENINE, BASED ON PALLADIUM-CATALYZED REDUCTION OF ALKENYL PHOSPHATES Reviewed
Haruhiko Fuwa, Makoto Sasaki
HETEROCYCLES 76 ( 1 ) 521 - 539 2008.9
An efficient strategy for the synthesis of endocyclic enol ethers and its application to the synthesis of spiroacetals Reviewed
Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 10 ( 12 ) 2549 - 2552 2008.6
Stereocontrolled synthesis of the A/B-ring fragment of gambieric acid B: Reassignment of the absolute configuration of the polycyclic ether region Reviewed
Haruhiko Fuwa, Tomomi Goto, Makoto Sasaki
ORGANIC LETTERS 10 ( 11 ) 2211 - 2214 2008.6
Total synthesis of (-)-brevenal: A concise synthetic entry to the pentacyclic polyether core Reviewed
Makoto Ebine, Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 10 ( 11 ) 2275 - 2278 2008.6
Convergent strategies for the total synthesis of polycyclic ether marine metabolites Reviewed
Makoto Sasaki, Haruhiko Fuwa
NATURAL PRODUCT REPORTS 25 ( 2 ) 401 - 426 2008
Total synthesis of (+)-neopeltolide Reviewed
Haruhiko Fuwa, Shinya Naito, Tomomi Goto, Makoto Sasaki
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 ( 25 ) 4737 - 4739 2008
Recent advances in the synthesis of marine polycyclic ether natural products Reviewed
Haruhiko Fuwa, Makoto Sasaki
CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT 10 ( 6 ) 784 - 806 2007.11
Strategies for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates Reviewed
Haruhiko Fuwa, Makoto Sasaki
ORGANIC LETTERS 9 ( 17 ) 3347 - 3350 2007.8
Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors Reviewed
Haruhiko Fuwa, Yasuko Takahashi, Yu Konno, Naoto Watanabe, Hiroyuki Miyashita, Makoto Sasaki, Hideaki Natsugari, Toshiyuki Kan, Tohru Fukuyama, Taisuke Tomita, Takeshi Iwatsubo
ACS CHEMICAL BIOLOGY 2 ( 6 ) 408 - 418 2007.6
Stereoselective synthesis of the AB-ring fragment of gambieric acid A Reviewed
Haruhiko Fuwa, Akihiro Suzuki, Kazushi Sato, Makoto Sasaki
HETEROCYCLES 72 ( 1 ) 139 - 144 2007.4
An efficient method for the synthesis of enol ethers and enecarbamates. Total syntheses of isoindolobenzazepine alkaloids, lennoxamine and chilenine Reviewed
Haruhiko Fuwa, Makoto Sasaki
ORGANIC & BIOMOLECULAR CHEMISTRY 5 ( 12 ) 1849 - 1853 2007
A strategy for the synthesis of 2,3-disubstituted indoles starting from N-(o-halophenyl)allenamides Reviewed
Haruhiko Fuwa, Makoto Sasaki
ORGANIC & BIOMOLECULAR CHEMISTRY 5 ( 14 ) 2214 - 2218 2007
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-phosphono enecarbamates Reviewed
Haruhiko Fuwa, Makoto Sasaki
CHEMICAL COMMUNICATIONS ( 27 ) 2876 - 2878 2007
Concise and short synthesis of functionalized 5,6-dihydropyridin-2-ones by means of palladium(0)-catalyzed cross-coupling of ketene aminal phosphates Reviewed
Haruhiko Fuwa, Akane Kaneko, Yasuaki Sugimoto, Taisuke Tomita, Takeshi Iwatsubo, Makoto Sasaki
HETEROCYCLES 70 ( 1 ) 101 - + 2006.12
Total synthesis, structure revision, and absolute configuration of (-)-brevenal Reviewed
Haruhiko Fuwa, Makoto Ebine, Andrea J. Bourdelais, Daniel G. Baden, Makoto Sasaki
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 ( 51 ) 16989 - 16999 2006.12
39 Total Synthesis and Structural Revision of Marine Polyether Natural Product Brevenal
Fuwa Haruhiko, Ebine Makoto, Ishioka Hiroki, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 48 ) 229 - 234 2006.9
Effect of ciguatoxin 3C on voltage-gated Na+ and K+ currents in mouse taste cells Reviewed
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 2006.9
Synthesis of biotinylated photoaffinity probes based on arylsulfonamide gamma-secretase inhibitors Reviewed
Haruhiko Fuwa, Kenichi Hiromoto, Yasuko Takahashi, Satoshi Yokoshima, Toshiyuki Kan, Tohru Fukuyama, Takeshi Iwatsubo, Taisuke Tomita, Hideaki Natsugari
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 16 ( 16 ) 4184 - 4189 2006.8
Total synthesis of the proposed structure of brevenal Reviewed
Haruhiko Fuwa, Makoto Ebine, Makoto Sasaki
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 ( 30 ) 9648 - 9650 2006.8
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 Reviewed
Makoto Sasaki, Naoki Takeda, Haruhiko Fuwa, Ryulchi Watanabe, Masayuki Satake, Yasukatsu Oshima
TETRAHEDRON LETTERS 47 ( 32 ) 5687 - 5691 2006.8
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" 2006.7
Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates Reviewed
Yasuko Takahashi, Haruhiko Fuwa, Akane Kaneko, Makoto Sasaki, Satoshi Yokoshima, Hifumi Koizumi, Tohru Takebe, Toshiyuki Kan, Takeshi Iwatsubo, Taisuke Tomita, Hideaki Natsugari, Tohru Fukuyama
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 16 ( 14 ) 3813 - 3816 2006.7
Divergent synthesis of multifunctional molecular probes based on caprolactam-derived γ-secretase inhibitors and their molecular targets
H. Fuwa
Abstracts of 25th IUPAC International Conference on Biodiversity and Natural Products 2006.7
C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) Reviewed
Yuichi Morohashi, Toshiyuki Kan, Yusuke Tominari, Haruhiko Fuwa, Yumiko Okamura, Naoto Watanabe, Chihiro Sato, Hideaki Natsugari, Tohru Fukuyama, Takeshi Iwatsubo, Taisuke Tomita
JOURNAL OF BIOLOGICAL CHEMISTRY 281 ( 21 ) 14670 - 14676 2006.5
The sodium channel of human excitable cells is a target for gambierol Reviewed
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
Synthesis and biological evaluation of gambierol analogues: Efforts toward the development of biotinylated photoaffinity labeling probes
H. Fuwa
Abstracts of PACIFICHEM2005 2005.12
Inhibition of voltage-gated potassium currents by gambierol in mouse taste cells Reviewed
Ghiaroni, V, M Sasaki, H Fuwa, GP Rossini, G Scalera, T Yasumoto, P Pietra, A Bigiani
TOXICOLOGICAL SCIENCES 85 ( 1 ) 657 - 665 2005.5
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 Reviewed
H Fuwa, T Kobayashi, T Tokitoh, Y Torii, H Natsugari
TETRAHEDRON 61 ( 17 ) 4297 - 4312 2005.4
Intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-ones and its application to the synthesis of secondary aryl amines Reviewed
H Fuwa, T Kobayashi, T Tokitoh, Y Torii, H Natsugari
SYNLETT ( 14 ) 2497 - 2500 2004.11
64(P-47) Diverted Total Synthesis and Biological Evaluation of Gambierol Analogues
Fuwa Haruhiko, Natsugari Hideaki, Kainuma Noriko, Tachibana Kazuo, Satake Masayuki, Sasaki Makoto
Symposium on the Chemistry of Natural Products, symposium papers ( 46 ) 359 - 364 2004.10
Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity Reviewed
H Fuwa, N Kainuma, K Tachibana, C Tsukano, M Satake, M Sasaki
CHEMISTRY-A EUROPEAN JOURNAL 10 ( 19 ) 4894 - 4909 2004.10
Total synthesis of polycyclic ether natural products based on Suzuki-Miyaura cross-coupling Reviewed
M Sasaki, H Fuwa
SYNLETT ( 11 ) 1851 - 1874 2004.9
Synthetic studies on antascomicin A: construction of the C18-C34 fragment Reviewed
H Fuwa, Y Okamura, H Natsugari
TETRAHEDRON 60 ( 25 ) 5341 - 5352 2004.6
Convergent synthesis of the ABCDE ring fragment of ciguatoxins Reviewed
H Fuwa, S Fujikawa, K Tachibana, H Takakura, M Sasaki
TETRAHEDRON LETTERS 45 ( 24 ) 4795 - 4799 2004.6
Highly efficient synthesis of medium-sized lactams via intramolecular Staudinger-aza-Wittig reaction of omega-azido pentafluorophenyl ester: synthesis and biological evaluation of LY411575 analogues Reviewed
H Fuwa, Y Okamura, Y Morohashi, T Tomita, T Iwatsubo, T Kan, T Fukuyama, H Natsugari
TETRAHEDRON LETTERS 45 ( 11 ) 2323 - 2326 2004.3
Pathological effects on mice by gambierol, possibly one of the ciguatera toxins Reviewed
E Ito, F Suzuki-Toyota, K Toshimori, H Fuwa, K Tachibana, M Satake, M Sasaki
TOXICON 42 ( 7 ) 733 - 740 2003.12
Synthesis and biological evaluation of gambierol analogues Reviewed
H Fuwa, N Kainuma, M Satake, M Sasaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 13 ( 15 ) 2519 - 2522 2003.8
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 2003.8
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 2003.7
不破春彦, 佐々木誠
化学 58 ( 5 ) 32 - 37 2003.5
Total synthesis of (-)-gambierol Reviewed
H Fuwa, N Kainuma, K Tachibana, M Sasaki
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 124 ( 50 ) 14983 - 14992 2002.12
27 Total Synthesis of Gambierol
Fuwa Haruhiko, Sasaki Makoto, Tachibana Kazuo
Symposium on the Chemistry of Natural Products, symposium papers ( 44 ) 157 - 162 2002.9
Total synthesis of gambierol Reviewed
H Fuwa, M Sasaki, M Satake, K Tachibana
ORGANIC LETTERS 4 ( 17 ) 2981 - 2984 2002.8
A general strategy for the convergent synthesis of fused polycyclic ethers via B-alkyl Suzuki coupling: synthesis of the ABCD ring fragment of ciguatoxins Reviewed
M Sasaki, M Ishikawa, H Fuwa, K Tachibana
TETRAHEDRON 58 ( 10 ) 1889 - 1911 2002.3
Synthetic studies toward gambierol. Convergent synthesis of the octacyclic polyether core Reviewed
H Fuwa, M Sasaki, K Tachibana
ORGANIC LETTERS 3 ( 22 ) 3549 - 3552 2001.11
Synthetic studies on a marine polyether toxin, gambierol: stereoselective synthesis of the EFGH ring system via B-alkyl Suzuki coupling Reviewed
H Fuwa, M Sasaki, K Tachibana
TETRAHEDRON 57 ( 15 ) 3019 - 3033 2001.4
Synthetic studies on a marine polyether toxin, gambierol: stereoselective synthesis of the FGH ring system via B-alkyl Suzuki coupling Reviewed
H Fuwa, M Sasaki, K Tachibana
TETRAHEDRON LETTERS 41 ( 43 ) 8371 - 8375 2000.10
Convergent synthesis of an HIJK ring model of ciguatoxin via Suzuki cross-coupling reaction Reviewed
M Sasaki, K Noguchi, H Fuwa, K Tachibana
TETRAHEDRON LETTERS 41 ( 9 ) 1425 - 1428 2000.2
A general method for convergent synthesis of polycyclic ethers based on Suzuki cross-coupling: Concise synthesis of the ABCD ring system of ciguatoxin Reviewed
M Sasaki, H Fuwa, M Ishikawa, K Tachibana
ORGANIC LETTERS 1 ( 7 ) 1075 - 1077 1999.10
New strategy for convergent synthesis of trans-fused polyether frameworks based on palladium-catalyzed Suzuki cross-coupling reaction Reviewed
M Sasaki, H Fuwa, M Inoue, K Tachibana
TETRAHEDRON LETTERS 39 ( 49 ) 9027 - 9030 1998.12
Modern Natural Product Synthesis
H. Fuwa（ Role： ContributorPursuing Step Economy in Total Synthesis of Complex Marine Macrolide Natural Products）
Springer, Singapore 2024.5 （ ISBN:9789819716197 ）
Marine Natural Products (Topics in Heterocyclic Chemistry, vol. 58)
T. Sugai, H. Fuwa（ Role： ContributorTotal Synthesis of (−)-Enigmazole A）
Springer, Singapore 2020.11
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（ Role： Contributor13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 2018.3
Strategies and Tactics in Organic Synthesis (Vol. 12)
H. Fuwa（ Role： Contributor(−)-Lyngbyaloside B, a Marine Macrolide Glycoside: Total Synthesis and Stereochemical Revision）
Elsevier 2016
Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, 3rd Edition
edited by Luis, M, Botana,eds（ Role： Joint authorGambierol: Synthetic aspects）
CRC Press 2014.3
Toxins and Biologically Active Compounds from Marine Microalgae
edeted by Gian, Paolo Rossini（ Role： Joint authorTotal synthesis of marine polycyclic ether natural products）
CRC Press 2014.2
天然物合成で活躍した反応「実験のコツとポイント」
（ Role： Joint author鈴木ー宮浦カップリング）
化学同人 有機合成化学協会編 2011.10
Total Synthesis of (−)-Exiguolide, a Potent Anticancer Marine Macrolide Invited Reviewed
Haruhiko Fuwa
HETEROCYCLES 104 ( 10 ) 1709 - 1709 2022.7
Structure determination, correction, and disproof of marine macrolide natural products by chemical synthesis Invited Reviewed
H. Fuwa
Organic Chemistry Frontiers 8 3990 - 4023 2021.7
Synthesis-driven stereochemical assignment of marine polycyclic ether natural products Invited Reviewed
H. Fuwa
Marine Drugs 19 257 2021.4
タンデム反応と複雑天然物の全合成 Invited
村田佳亮, 不破春彦
化学工業 71 117 - 124 2020.2
Total Synthesis of a Marine Macrolide Natural Product, Iriomoteolide-2a: The Fundamental Role of Total Synthesis in Natural Product Chemistry Invited Reviewed
Keita Sakamoto, Haruhiko Fuwa
Journal of Synthetic Organic Chemistry, Japan 77 ( 8 ) 831 - 840 2019.8
Total Synthesis and Chemical Biology of Marine Macrolide Natural Products
67 ( 9 ) 668 - 675 2016.9
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
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
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
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
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
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 2004.7
Synthesis and biological evaluation of LY411575 analogues
H. Fuwa
Abstracts of 2nd World Congress of Pharmaceutical Society 2004.5
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
Total synthesis of a marine polyether toxin, gambierol
Haruhiko Fuwa, Makoto Sasaki
Journal of Synthetic Organic Chemistry, Japan 61 ( 8 ) 742 - 751 2003.8
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 2021.9
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 ) 2019.8 有機合成化学協会関西支部
タンデム反応を基盤とした新合成法の開発 Invited
不破春彦
第9回有機分子構築法夏の勉強会 ( 湯河原 ) 2019.5
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 ) 2018.7 公益財団法人旭硝子財団
Total synthesis, stereochemical revision, and biological evaluation of lyngbyaloside B, a marine macrolide glycoside International conference
H. Fuwa, Y. Okuaki, N. Yamagata, M. Sasaki
Abstracts of PACIFICHEM2015 ( Honolulu, Hawaii ) 2015.12 PACIFICHEM2015
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 2015.9
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 2015.9
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」 2015.3
Synthetic and structural studies on lyngbyaloside B, a cytotoxic marine macrolide glycoside International conference
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2014.10 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」
Studies toward the total synthesis of iriomoteolide-2a International conference
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2013.10 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」
Total synthesis and biological evaluation of marine macrolide natural products International conference
H. Fuwa
Abstracts of the 70th Anniversary Symposium of the Chemical Society of Japan Tohoku Branch 2013.9 日本化学会東北支部
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 2013.5
Total synthesis and structure-activity relationships of marine macrolide natural products International conference
H. Fuwa
Abstracts of International Symposium on Chemical Biology of Natural Products 2012.10 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」
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 2012.9
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 2011.11
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 2011.8
Total synthesis and biological assessment of (–)-exiguolide and analogues International conference
H. Fuwa
Asian International Symposium 2011.3 日本化学会
Concise total synthesis of (+)-neopeltolide International conference
H. Fuwa, A. Saito, M. Sasaki
Abstracts of PACIFICHEM2010 ( Honolulu, Hawaii ) 2010.12 PACIFICHEM2010
(-)-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 2010.10
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 2010.3
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 2009.9
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 2008.3
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 2007.7
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 2006.10
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 2006.9
Divergent synthesis of multifunctional molecular probes based on caprolactam-derived γ-secretase inhibitors and their molecular targets International conference
H. Fuwa
Abstracts of 25th IUPAC International Conference on Biodiversity and Natural Products ( Kyoto ) 2006.7 International Union of Pure and Applied Chemistry
Synthesis and biological evaluation of gambierol analogues: Efforts toward the development of biotinylated photoaffinity labeling probes International conference
H. Fuwa
Abstracts of PACIFICHEM2005 ( Honolulu, Hawaii ) 2005.12 PACIFICHEM2005
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 2005.7
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 2005.3
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 2002.11
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 2002.10
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 2002.3
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 2001.3
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 2000.3
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 1999.11
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 1999.6
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 1998.9
令和6年度手島精一記念研究賞 研究論文賞
2025.3 東京科学大学
科学技術分野の文部科学大臣表彰若手科学者賞
2011.4 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
2010.3 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）
2008.10 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
2004.7 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）
2002.10 天然有機化合物討論会 ガンビエロールの全合成
計算化学が先導する複雑大員環天然物の構造決定と全合成の高効率化
Grant number：25K01906 2025.4 - 2028.3
日本学術振興会 科学研究費助成事業 基盤研究(B) 中央大学
不破 春彦
Authorship：Principal investigator
Grant amount： \18720000 （ Direct Cost: \14400000 、 Indirect Cost： \4320000 ）
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
2022.4 - 2025.3
日本学術振興会 基盤研究(C)
不破 春彦
Grant type：Competitive
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
2021.4 - 2025.3
基盤研究(B)
津田正史
Grant type：Competitive
超活性抗腫瘍性海洋天然物の全合成研究
2019.10 - 2020.9
山田科学振興財団 研究援助
不破 春彦
Authorship：Principal investigator Grant type：Competitive
Grant amount： \2000000 （ Direct Cost: \2000000 ）
Total Synthesis, Structure Determination, and Bioactive Stereostructure of Complex Macrolides
Grant number：17K01941 2017.4 - 2020.3
日本学術振興会 Grants-in-Aid for Scientific Research 基盤研究(C) Chuo University
不破 春彦
Authorship：Principal investigator Grant type：Competitive
Grant amount： \4680000 （ Direct Cost: \3600000 、 Indirect Cost： \1080000 ）
Total synthesis of the proposed structure of iriomoteolide-2a has been achieved. Our synthesis involved: 1) convergent assembly of important fragments via a Suzuki-Miyaura reaction and an esterification, and 2) forging the macrocyclic skeleton by means of a ring-closing metathesis. However, the NMR spectra of our synthetic material did not match those of natural iriomoteolide-2a. Synthesis/NMR analysis of model compounds and careful inspection of the NMR data of the authentic sample, followed by total syntheses of possible structures enabled us to determine the absolute configuration of iriomoteolide-2a.
Total synthesis of enigmazole A has been completed. The salient features of our synthesis include: 1) a stereoselective tandem synthesis of the tetrahydropyran ring, 2) a Au(I)-catalyzed Meyer-Schuster rearrangement of a propargylic benzoate, and 3) a macrocyclic ring-closing metathesis.
Total Synthesis of Complex Marine Natural Products Based on Tandem Reactions
2018.12 - 2019.11
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
Authorship：Principal investigator Grant type：Competitive
Grant amount： \3000000 （ Direct Cost: \3000000 ）
Development and Application of New Synthetic Strategy toward Marine Macrolides
2018.4 - 2019.3
東京応化科学技術振興財団 研究費の助成
不破 春彦
Authorship：Principal investigator Grant type：Competitive
Grant amount： \1000000 （ Direct Cost: \1000000 ）
Total Synthesis, Complete Stereostructure. and Structure-Activity Relationship of Complex Macrocyclic Natural Products
2016.11 - 2017.10
住友財団 基礎科学研究助成
不破 春彦
Authorship：Principal investigator Grant type：Competitive
Grant amount： \1300000 （ Direct Cost: \1300000 ）
Total Synthesis and Structure-Activity Relationship of Complex Natural Product That Exhibits Selective Cytotoxicity Against Cells Expressing Mutant c-Kit
2015.4 - 2017.3
旭硝子財団 第１分野（化学・生命科学系）研究奨励
不破 春彦
Authorship：Principal investigator Grant type：Competitive
Grant amount： \2000000 （ Direct Cost: \2000000 ）
Synthesis and functional analysis of novel biologically active molecules based on complex macrolide natural products
Grant number：25282228 2013.4 - 2017.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Tohoku University
Sasaki Makoto, FUWA Haruhiko
Grant amount： \18590000 （ Direct Cost: \14300000 、 Indirect Cost： \4290000 ）
Our research focused on the efficient total synthesis of structurally complex marine macrolide natural products with significant biological activities to investigate and exploit their biological functions. A convergent synthesis of a fully functionalized macrolactone core of goniodomin A, a polyether macrolide that targets actin cytoskeleton, has been accomplished. An efficient, convergent total synthesis of polycavernoside B, a lethal glycosidic macrolide isolated from the red alga, has been achieved for the first time. In addition, efficient synthetic routes to the C1-C13 and C8-C29 fragments of amphidinolide N, an extremely potent cytotoxic macrolide, have been developed in a convergent manner.
微量複雑海洋天然物の合理的構造単純化及び作用解析
Grant number：26102708 2014.4 - 2016.3
日本学術振興会 科学研究費助成事業 新学術領域研究(研究領域提案型) 東北大学
不破 春彦
Grant amount： \5330000 （ Direct Cost: \4100000 、 Indirect Cost： \1230000 ）
本年度は前年度に引き続き，複雑海洋天然物イリオモテオリド-2aの全合成研究を行った。昨年度末までに，イリオモテオリド-2a提出構造式には帰属の誤りがあることが明らかとなった。そこで，本天然物に含まれる不斉炭素原子の立体配置の帰属を再検証することにした。合成品と天然標品のNMRスペクトルデータを比較した結果，C12/C13の相対配置の帰属に誤りがあり，C13位を起点に相対配置が決定されたC15及びC16位の立体配置も誤っているものと考えた。
以上の経緯から，提出構造式の13,15,16-epi体を新たなターゲット分子に設定した。この際，ビステトラヒドロフラン部分構造は，Sharpless不斉エポキシ化とエポキシド連続環化反応を一挙に達成する新しい戦略で立体選択的に構築することに成功した。その後は提出構造式の全合成法に則り，13,15,16-epi体の全合成を達成した。しかしまたも，合成品の1H及び13C NMRスペクトルデータは天然標品のそれと一致しなかった。
<BR>
本年度はまた複雑海洋天然物ネオペルトリドの蛍光標識プローブを創出し，生細胞における局在解析を行った。独自の構造活性相関解析の知見を踏まえ，8,9-デヒドロネオペルトリド(8,9-DNP)のC11位を修飾して蛍光色素を連結させ，数種の蛍光標識プローブを取得した。細胞増殖阻害試験と生細胞染色試験でプローブを評価した結果，BODIPY-FLを導入した8,9-DNP-BODIPYが最も優れたパフォーマンスを示した。8,9-DNP-BODIPYとオルガネラマーカーによる生細胞二重染色試験を行った結果，本化合物は主として小胞体に速やかに集積し，親化合物である8,9-DNPにより蛍光染色が競争的に阻害された。領域内の共同研究者による線虫初期胚の染色実験でも同様の結果が得られた。
Synthesis and functional analysis of ion channel selective inhibitors based on polycyclic ethers
Grant number：23102016 2011.4 - 2016.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area) Tohoku University
Sasaki Makoto, FUWA HARUHIKO, KONOKI KEIICHI
Grant amount： \34580000 （ Direct Cost: \26600000 、 Indirect Cost： \7980000 ）
Gambierol is a structurally complex marine polycyclic ether natural product that exhibits potent inhibitory activity against voltage-gated potassium ion channels (Kv channels) with specific subtype selectivity. In order to clarify skeletal structure-activity relationship, hepta-, tetra-, and tricyclic analogues of gambierol were synthesized and tested for inhibitory activity against Kv1.2 channel, which was stably expressed in Chinese hamster ovary (CHO) cells. It was revealed that tetracyclic analogue of gambierol comprising the right-hand EFGH-ring with a triene side chain is the minimal structural unit for inhibitory activity against Kv1.2 channels. Furthermore, we designed and synthesized photoaffinity probe based on the structure of the tetracyclic analogue to identify the binding site of the ligand on Kv channels.
実用的全合成に立脚した微量複雑海洋天然物ケミカルバイオロジー
Grant number：24102507 2012.4 - 2015.3
日本学術振興会 科学研究費助成事業 新学術領域研究(研究領域提案型) 東北大学
不破 春彦
Grant amount： \6370000 （ Direct Cost: \4900000 、 Indirect Cost： \1470000 ）
本年度は，渦鞭毛藻Amphidinium sp.の培養藻体から単離・構造決定されたイリオモテオリド-2aのC6-C18ビステトラヒドロフラン部分構造及びC19-C28側鎖構造の立体選択的でスケーラブルな合成法の確立を行った。
C9位の不斉中心の制御には，野上らが開発した不斉アリルトランスファー反応を用いることで，C6-C11部分構造のスケールアップを容易にした。一方，C12-C18部分構造は市販のベンジル(S)-グリシジルエーテルを原料とし，既報の手法に従い合成した。得られた両部分構造をオレフィン交差メタセシス反応により連結した後，C11位の不斉中心をCBS還元により，C12, C13位不斉中心はSharpless不斉エポキシ化反応によりを制御した。続いて2つのテトラヒドロフラン環の立体特異的な構築を行った。C9位ヒドロキシ基の脱保護と続く弱酸処理により，C9-C12テトラヒドロフランはヒドロキシエポキシドの分子内環化反応により構築した。生じたC13位ヒドロキシ基をメシル化した後，塩基性条件下でC16位ベンゾイルオキシ基の脱保護と分子内環化を一挙に行い，C13-C16テトラヒドロフラン環を構築した。
一方，C19-C28側鎖構造は(R)-リンゴ酸を出発原料とし，Seebachアルキル化，野崎ー檜山ー岸反応，Brown不斉アリル化反応を鍵段階とする直裁的な合成法により，数百ミリグラムオーダーで合成した。
以上，イリオモテオリド-2aの構造的特徴であるC6-C18ビステトラヒドロフラン部分構造及びC19-C28側鎖構造に関する，高立体選択的かつスケーラブルな合成法の開発に成功した。当該部分構造のスケーラブルな合成法は，天然物そのものに限らず，類縁体や標識化合物の合成に不可欠で，イリオモテオリド-2aの全合成とケミカルバイオロジー研究を大きく前進させる成果と考えられる。
Unified Total Synthesis and Structure-Activity Relationships of Marine Macrolide Natural Products of Cyanobacteria Origin
Grant number：23681045 2011.4 - 2014.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A) Tohoku University
FUWA Haruhiko
Grant amount： \26000000 （ Direct Cost: \20000000 、 Indirect Cost： \6000000 ）
This project pursued unified total synthesis and structure-activity relationships of marine macrolide natural products of cyanobateria origin. Our concise synthesis of neopeltolide, a highly potent antiproliferative macrolide, enabled us to elucidate its pharmacophoric structural elements required for potent activity. Several truncated neopeltolide analogues with nanomolar activity were successfully designed on the basis of our pharmacophore model. Concise total synthesis of lyngbyaloside B, a moderately cytotoxic macrolide glycoside, and its 13-demethyl analogue was also achieved. Design, synthesis, and biological evaluation of chimeric macrolides were undertaken to show that polyketide macrolides offer unique structural motifs useful for the development of novel antiproliferative agents.
Mechanisms of an anti-cancer effect of a novel marine natural compound, exiguolide.
Grant number：23659427 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Tohoku University
KUBO Hiroshi
Grant amount： \3640000 （ Direct Cost: \2800000 、 Indirect Cost： \840000 ）
The aim of this experiment is to elucidate the mechanisms of an anti-cancer effect of a novel marine natural compound, exiguolide. The cell cycle of cultured cancer cells was arrested with apoptotic cells death under incubation with exiguolide. Tumor growth was also attenuated by the treatment with exiguolide in the in vivo xenograft model in mice. Several kinases were involved in this anti-cancer effect. Then, we synthesized exiguolide analogues with modified structures. Some of the analogues had a similar anti-cancer effect in both in vitro and in vivo. These results will bring the basis for developing a new anti-cancer drug, which can be clinically applicable.
Total Synthesis and Functional Analysis of Complex Natural Products
Grant number：21241050 2009 - 2011
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Tohoku University
SASAKI Makoto, FUWA Haruhiko, KONOKI Keiichi
Grant amount： \26780000 （ Direct Cost: \20600000 、 Indirect Cost： \6180000 ）
Efficient synthetic routes to architecturally complex natural products with potent biological activities and molecular weights over 500 have been developed for exploring their biological functions. In particular, the first total synthesis and complete stereostructure determination of gambieric acid A have been accomplished. An efficient total synthesis of polycavernoside A has been also achieved in a convergent approach. In addition, efficient synthetic routes to the C1. C16 and C12. C36 fragments of goniodomin A have been developed by exploiting Stille-type coupling of thioesters.
Total synthesis of a natural HIV protease inhibitor and its partial structures
Grant number：21710216 2009 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Tohoku University
FUWA Haruhiko
Grant amount： \4290000 （ Direct Cost: \3300000 、 Indirect Cost： \990000 ）
HIV protease is an enzyme responsible for the proteolysis of the polyprotein expressed by the retrovirus to produce matured proteins necessary for proliferation and infection. Thus, the inhibition of HIV protease represents an important therapeutic strategy for HIV-infected patients. In the present study, we have investigated synthetic routes toward marine natural products didemnaketals and their partial structures. We have completed the stereoselective syntheses of the C1-C11 acyclic domain and C9-C28 spiroacetal domain of didemnaketal B.
Development of new strategies for the synthesis of nitrogen heterocycles and its application to the search for γ-secretase inhibitors
Grant number：19710177 2007 - 2008
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Tohoku University
FUWA Haruhiko
Grant amount： \2810000 （ Direct Cost: \2600000 、 Indirect Cost： \210000 ）
グルタミン酸受容体サブタイプ選択的な生体機能分子の創製と機能解析
Grant number：16073202 2004 - 2007
日本学術振興会 科学研究費助成事業 特定領域研究 東北大学
佐々木 誠, 及川 雅人, 不破 春彦, 酒井 隆一, 島本 啓子
Grant amount： \57300000 （ Direct Cost: \57300000 ）
グルタミン酸受容体は高等動物の中枢神経シナプスにおいて興奮性神経伝達の中心的役割を司るのみならず、記憶や学習などの高次脳機能、種々の脳疾患における神経細胞死に深く関与している。グルタミン酸受容体は数多くのサブタイプに細分化されているが、個々の生理機能は未だ完全には明らかにされていない。本研究では、グルタミン酸受容体サブタイプ選択的なアゴニストである海綿由来の興奮性アミノ酸ダイシハーベインおよびネオダイシハーベインAとそれらの類縁体の効率的全合成と構造展開により、サブタイプ選択的な生体機能分子の創製と機能解析を目的とした。
ネオダイシハーベインA類縁体全合成における重要中間体から、N-Boc保護1,2-アミノアルコールの分子内S_N2環化反応により6員環上の官能基導入を行い、ダイシハーベインの全合成を達成した。さらに、ヨードアミノ環化によるC8位アミノ基の立体選択的導入法を開発し、より効率的な全合成ルートを確立した。
ダイシハーベインおよびネオダイシハーベインAとGluR5カイニン酸受容体リガンド結合ドメインとの複合体のX線結晶構造解析に初めて成功し、原子レベルでその結合様式を明らかにした。
上記合成ルートを利用して、ダイシハーベイン類縁体を合成し、構造活性相関研究の結果からC9α水酸基が受容体との結合に重要であることが示唆された。また、ネオダイシハーベインAの構造類縁体について詳細な生物活性評価を行い、2,4-エピ体がGluR5およびGluR6カイニン酸受容体に対する機能的アンタゴニストとして機能する初めての化合物であることを明らかにした。
中員環ラクタムの効率的構築法の開発とそのγセクレターゼ阻害剤探索研究への応用
Grant number：16710154 2004 - 2006
日本学術振興会 科学研究費助成事業 若手研究(B) 東京大学
不破 春彦
Grant amount： \2300000 （ Direct Cost: \2300000 ）
アルツハイマー病(AD)による死亡者は全世界で年間数百万人とも報告されており、その根治療法の確立は現代医学において解決すべき急務の課題である。ADの発症機構として提唱されているアミロイドβ(Aβ)仮説によれば、アスパラギン酸プロテアーゼであるγセクレターゼの機能を阻害しAβ産生を抑制するアプローチが、根治療法開発の一つの切り口である。米国EliLilly社が開発したγセクレターゼ阻害剤LY411575は、最も強力にAβ産生を阻害する低分子の一つである。
本研究ではLY411575の構造的特徴である中員環ラクタムに着目し、その効率的構築法を検討した。既存の方法、すなわちBeckmannあるいはSchmidt転位では中員環ラクタムを収率良く得ることは困難であったが、ω-azidopentafluorophenyl esterの分子内Staudinger-aza-Wittig反応を用いると、多種多様な中員環ラクタムを効率的に構築できることを見出した。本反応の機構は次のように推察した:ホスフィンとアジド基とのStaudinger反応により生じたイミノホスホランが直ちに活性化エステルと分子内aza-Wittig反応を起こして不安定なイミノエーテルを生成し、これが加水分解を受けてラクタムが生じる。つぎに、LY411575の構造改変体の合成とそのAβ産生阻害活性の評価を行った。その結果、種々の置換基を導入しても、活性の低下を引き起こさない化学修飾に適切な部位が明らかとなり、適当なリンカーを介してベンゾフェノンやフルオレセインを導入した光親和性標識化プローブや蛍光プローブの開発にも成功した。現在、合成プローブを用いた有機化学レベルにおけるγセクレターゼの機能解析を検討している。
2020.5 - Now
Marine Drugs誌 編集委員
2022.3 - 2024.2
日本化学会 関東支部 常任幹事
2019.4 - 2021.3
有機合成化学協会 編集委員
2009.4 - 2015.12
有機合成化学協会東北支部 常任幹事
2007.10 - 2015.10
天然物化学談話会 世話人
2013.11 -
Frontiers in Chemistry誌 編集委員
Marine Drugs誌編集委員
Role(s)： Editer, Advisor, Planner
MDPI 2020.3 -
有機合成化学協会誌編集委員
Role(s)： Editer
有機合成化学協会 2019.3 -
