Synthetic study on biological active natural products by means of Ugi reaction

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390007
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: KAN Toshiyuki 静岡県立大学, 薬学部, 教授 (10221904)
• Co-Investigator(Kenkyū-buntansha): HAMASHIMA Yoshitaka 静岡県立大学, 薬学部, 教授 (40333900) ; ASAKAWA Tomohiro 静岡県立大学, 薬学部, 助教 (80571257)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: Ugi反応 / FR901483 / TAN1251A / イソニトリル

Research Abstract

The Ugi four-component condensation (Ugi 4CC) has been widely employed since it provides various alfa-amino amide derivatives by a simple experimental procedure under mild conditions. Recently, we have been developed novel isonitrile, which possessed odorless nature as well as readily convertible C-terminal amide of Ugi adducts. In this research, total synthesis of potent immunosuppressant FR901483 and TAN1251A, which possessed the subtype selective affinity against the muscarinic receptors have been accomplished by means of Ugi reaction with utilizing our novel isonitrile.

Research Products

• [Journal Article] Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats (2014)
  • Author(s): N. Yasuda, T. Ishii, D. Oyama, T. Fukuta, Y. Agato, A. Sato, K. Shimizu, T. Asai, T. Asakawa, T. Kan, S. Yamada, Y. Ohizumi, N. Oku
  • Journal Title: Brain Res Volume: 1559 Pages: 46-54
• [Journal Article] 2-Azahypoxanthine and imidazole-4-carboxamide produced by the fairy-ring-forming fungus increases wheat yield (2014)
  • Author(s): H. Tobina, J. Choi, T. Asai, Y. Kiriiwa, T. Asakawa, T. Kan, A. Morita, H. Kawagish
  • Journal Title: Field Crops Res Volume: 162 Pages: 6-11
• [Journal Article] Practical Total Syntheses of Acromelic Acids A and B (2014)
  • Author(s): H. Ouchi, A. Asahina, T. Asakawa, M. Inai, Y. Hamashima, T. Kan
  • Journal Title: Org. Lett Volume: 16 Pages: 1980-1983
• [Journal Article] Stereocontrolled Total Synthesis of Hedyotol A (2014)
  • Author(s): Y. Kawabe, R. Ishikawa, Y. Akao, A. Yoshida, M. Inai, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Org. Lett Volume: 16 Pages: 1976-1979
• [Journal Article] Enantioselective Synthesis of SB-203207 (2014)
  • Author(s): Y. Hirooka, K. Ikeuchi, Y. Kawamoto, Y. Akao, T. Furuta, T. Asakawa, M. Inai, T. Wakimoto, T. Fukuyama, T. Kan
  • Journal Title: Org. Lett Volume: 16 Pages: 1646-1649
• [Journal Article] Practical Synthesis of Kainoids : A New Chemical Probe Precursor and a Fluorescent Probe (2014)
  • Author(s): S. Sasaki, H. Suzuki, H. Ouchi, T. Asakawa, M. Inai, R. Sakai, K. Shimamoto, Y. Hamashima, T. Kan
  • Journal Title: Org. Lett Volume: 16 Pages: 564-567
• [Journal Article] The "Fairy" of Fairy Rings and Its Metabolite Exist in a Novel Purine Metabolic Pathway in Plants (2014)
  • Author(s): J. Choi, T. Ohnishi, Y. Yamakawa, S. Takeda, S. Sekiguchi, W. Maruyama, K. Yamashita, T. Suzuki, A. Morita, T. Ikka, R. Motohashi, Y. Kiriiwa, H. Tobina, T. Asai, S. Tokuyama, H. Hirai, N. Yasuda, K. Noguchi, T. Asakawa, S. Sugiyama, T. Kan, H. Kawagishi
  • Journal Title: Angew. Chem. Int. Ed Volume: 53 Pages: 1552
• [Journal Article] Use of positron emission tomography for real-time imaging of biodistribution of green tea catechin (2014)
  • Author(s): K. Shimizu, T. Asakawa, N. Harada, D. Fukumoto, H. Tsukada, T. Asai, S. Yamada, T. Kan, and N. Oku
  • Journal Title: PLOS ONE Volume: 9 Pages: e85520
• [Journal Article] Synthetic Studies of Fisetin, Myricetin and Nobiletin Analogs and Related Probe Molecules (2014)
  • Author(s): A. Hiza, Y. Tsukaguchi, T. Ogawa, M. Inai, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Heterocycles Volume: 88 Pages: 1371-1396
• [Journal Article] Stereocontrolled total synthesis of sphingofungin E (2013)
  • Author(s): K. Ikeuchi, M. Hayashi, T. Yamamoto, M. Inai, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Eur. J. Org. Chem Pages: 6789-6792
• [Journal Article] Physicochemical and biopharmaceutical characterization of amorphous solid dispersion of nobiletin, a citrus polymethoxylated flavone, with improved hepatoprotective effects (2013)
  • Author(s): S. Onoue, T. Nakamura, A. Uchida, K. Ogawa, K. Yuminoki, N. Hashimoto, A. Hiza, Y. Tsukaguchi, T. Asakawa, T. Kan, S. Yamada
  • Journal Title: Euro. J. Pharm. Sci Volume: 49 Pages: 453-460
• [Journal Article] Chemoselective Hydrogenation Reaction of Unsaturated Bonds in the Presence of o-Nitrobenzenesulfonyl Group (2013)
  • Author(s): A. Kawanishi, C. Miyamoto, Y. Yabe, M. Inai, T. Asakawa, Y. Hamashima, H. Sajiki, T. Kan
  • Journal Title: Org. Lett Volume: 15 Pages: 1306-1309
• [Journal Article] Synthesis of Theaflavins via Biomimetic Oxidative Coupling Reaction (2013)
  • Author(s): Y. Kawabe, Y. Aihara, Y. Hirose, A. Sakurada, A. Yoshida, M. Inai, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Synlett Pages: 479-482
• [Journal Article] Stereocontrolled Total Synthesis of (-)-FR-901483 (2012)
  • Author(s): S. Ieda, A. Masuda, M. Kariyama, T. Wakimoto, T. Asakawa, T. Fukuyama, T. Kan
  • Journal Title: Heterocycles Volume: 86 Pages: 1071-1092
• [Journal Article] Catalytic Desymmetrization of Cyclohexadienes by Asymmetric Bromolactonization (2012)
  • Author(s): K. Ikeuchi, S. Ido, S. Yoshimura, T. Asakawa, M. Inai, Y. Hamashima, T. Kan
  • Journal Title: Org. Lett Volume: 14 Pages: 6016-6019
• [Journal Article] Stereocontrolled Total Synthesis of (+)- UCS1025A (2012)
  • Author(s): K. Uchida, T. Ogawa, Y. Yasuda, H. Mimura, T. Fujimoto, T. Fukuyama, T. Wakimoto, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Angew. Chem., Int. Ed Volume: 51 Pages: 12850-12853
• [Journal Article] Total Synthesis of (-)-Lemonomycin (2012)
  • Author(s): A. Yoshida, M. Akaiwa, T. Asakawa, Y. Hamashima, S. Yokoshima, T. Fukuyama, T. Kan
  • Journal Title: Chem. Eur. J Volume: 18 Pages: 11192-11195
• [Journal Article] 3, 3', 4', 5, 5'-Pentahydroxyflavone is a potent inhibitor of amyloid fibril formation (2012)
  • Author(s): H. Ushikubo, S. Watanabe, Y. Tanimoto, K. Abe, A. Hiza, T. Ogawa, T. Asakawa, T. Kan, T. Akaishi
  • Journal Title: Neurosci. Lett Volume: 513 Pages: 51-56
• [Journal Article] A Short-step Asymmetric Synthesis of Dehydrodiconiferyl Alcohol via C-H Insertion Reaction (2012)
  • Author(s): S. Matsumoto, T. Asakawa, Y. Hamashima, T. Kan
  • Journal Title: Synlett Pages: 1082-1084
• [Journal Article] Furan Fatty Acid as an Anti-inflammatory Component from Green-Lipped Mussel, Perna canaliculus (2011)
  • Author(s): T. Wakimoto, H. Kondo, H. Nii, K. Kimura, Y. Egami, Y. Oka, M. Yoshida, E. Kida, Y. Ye, S. Akahoshi, T. Asakawa, K. Matsumura, H. Ishida, H. Nukaya, K. Tsuji, T. Kan, I. Abe
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Pages: 17533-17537
• [Journal Article] Enantioselective Total Synthesis of Aperidine (2011)
  • Author(s): T. Wakimoto, K. Miyata, H. Ouchi, T. Asakawa, H. Nukaya, Y. Suwa, T. Kan
  • Journal Title: Org. Lett Volume: 13 Pages: 2789-2791
• [Journal Article] Stereocntrolled Synthesis of (+)-Methoxyphenylkainic acid and (+)-Phenylkainic acid (2011)
  • Author(s): T. Higashi, Y. Isobe, H. Ouchi, H. Suzuki, Y. Okazaki, T. Asakawa T. Furuta, T. Wakimoto, T. Kan
  • Journal Title: Org. Lett Volume: 13 Pages: 1089-1091
• [Journal Article] PET Imaging Investigation of Nobiletin Based on a Practical Total Synthesis (2011)
  • Author(s): T. Asakawa, A. Hiza, M. Nakayama, M. Inai, D. Oyama, H. Koide, K. Shimizu, T. Wakimoto, N. Harada, H. Tsukada, N. Oku, T. Kan
  • Journal Title: Chem. Commun Volume: 47 Pages: 2868-2870
• [Journal Article] Anti-angiogenic activity and intracellular distribution of epigallalocatechin-3-gallate analogs (2011)
  • Author(s): S. PIYAVIRIYAKUL, K. Shimizu, T. Asakawa, T. Kan, P. SIRIPONG, N. Oku
  • Journal Title: Biol. Pharm. Bull Volume: 34 Pages: 396-400
• [Journal Article] Proof of the existence of an unstable amino acid, pleurocybellaziridine, in Pleurocybella porrigens (angel's wing mushroom) (2011)
  • Author(s): Toshiyuki Wakimoto, Tomohiro Asakawa, Saeko Akahoshi, Tomohiro Suzuki, Kaoru Nagai, Hirokazu Kawagishi, Toshiyuki Kan
  • Journal Title: Angew. Chem. Int. Ed Volume: 50 Pages: 1168-1170
• [Journal Article] Concise synthesis of catechin probes enabling analysis and imaging of EGCg (2011)
  • Author(s): A. Yoshida, Y. Hirooka, Y. Sugata, M. Nitta, T. Manabe, S. Ido, K. Murakami, R. K. Saha, T. Suzuki, M. Ohshima, A. Yoshida, K. Itoh, K. Shimizu, N. Oku, T. Furuta, T. Asakawa, T. Wakimoto, T. Kan
  • Journal Title: Chem. Commun Volume: 47 Pages: 1794-1796
• [Journal Article] Practical synthesis of natural plant-growth regulator 2-azahypoxanthine, its derivatives, and biotin-labeled probes
  • Author(s): K. Ikeuchi, R. Fujii, S. Sugiyama, T. Asakawa, M. Inai, Y. Hamashima, J. Choi, T. Suzuki, H. Kawagishi, T. Kan
  • Journal Title: Org. Biomol. Chem Volume: (in press)
• [Presentation] アクロメリン酸A, B の合成研究 (2013)
  • Author(s): 大内仁志, 朝比奈彩, 浅川倫宏, 稲井誠, 濱島義隆, 菅敏幸
  • Organizer: 第39回反応と合成の進歩シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2013-11-05
• [Presentation] (-)-Sphingofungin E の全合成 (2013)
  • Author(s): 池内和忠, 林萌未, 山本倫広, 稲井誠, 浅川倫宏, 濱島義隆, 菅敏幸
  • Organizer: 第55回天然有機化合物討論会
  • Place of Presentation: 京都
  • Year and Date: 2013-09-20
• [Presentation] アクロメリン酸B の全合成 (2013)
  • Author(s): 朝比奈彩, 大内仁志, 浅川倫宏, 稲井誠, 濱島義隆, 菅敏幸
  • Organizer: 第30回有機合成化学セミナー
  • Place of Presentation: 岡山
  • Year and Date: 2013-09-18
• [Presentation] アクロメリン酸A の全合成 (2013)
  • Author(s): 大内仁志, 浅川倫宏, 稲井誠, 濱島義隆, 菅敏幸
  • Organizer: 第103回有機合成シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-06-05
• [Presentation] アクロメリン酸類の合成研究 (2013)
  • Author(s): 朝比奈彩, 大内仁志, 浅川倫宏, 稲井誠, 濱島義隆, 菅敏幸
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] TAN1251C の合成研究 (2013)
  • Author(s): 長坂洋祐, 升田明孝, 苅山真美, 稲井誠, 浅川倫宏, 濱島義隆, 菅敏幸
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] アクロメリン酸A の実用的合成法の開発 (2013)
  • Author(s): 大内仁志, 浅川倫宏, 稲井誠, 濱島義隆, 菅敏幸
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] (-)-Sphingofungin E の全合成 (2013)
  • Author(s): 池内和忠, 林萌未, 山本倫広, 稲井誠, 浅川倫宏, 濱島義隆, 菅敏幸
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] Sphingofungin E の全合成 (2012)
  • Author(s): 池内和忠, 林 萌未, 井戸俊輔, 山本倫広, 稲井 誠, 浅川倫宏, 濱島義隆, 菅 敏幸
  • Organizer: 第10回次世代を担う有機化学シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 20120511-12
• [Presentation] TAN1251C の合成研究 (2012)
  • Author(s): 長坂洋祐, 升田明孝, 岩永耕治, 浅川倫宏, 濱島義隆, 横島 聡, 福山 透, 菅 敏幸
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会
  • Place of Presentation: 岐阜
  • Year and Date: 2012-11-18
• [Presentation] (-)-レモノマイシンの全合成 (2012)
  • Author(s): 吉田篤史, 赤岩路則, 濱島義隆, 横島 聡, 福山 透, 菅敏幸
  • Organizer: 第54回天然有機化合物討論会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-20
• [Presentation] (-)-レモノマイシンの全合成 (2012)
  • Author(s): 吉田篤史, 赤岩路則, 濱島義隆, 横島 聡, 福山 透, 菅敏幸
  • Organizer: 第29回有機合成化学セミナー
  • Place of Presentation: 静岡
  • Year and Date: 2012-09-06
• [Presentation] Sphingofungin E の不斉合成研究 (2012)
  • Author(s): 池内和忠, 林 萌未, 井戸俊輔, 山本倫広, 稲井 誠, 浅川倫宏, 濱島義隆, 菅 敏幸
  • Organizer: 第29回有機合成化学セミナー
  • Place of Presentation: 静岡
  • Year and Date: 2012-09-06
• [Presentation] アクロメリン酸の触媒的不斉合成 (2012)
  • Author(s): 大内仁志, 濱島義隆, 袖岡幹子, 浅川倫宏, 稲井誠, 菅 敏幸
  • Organizer: 第29回有機合成化学セミナー
  • Place of Presentation: 静岡
  • Year and Date: 2012-09-06
• [Presentation] TAN1251C の全合成 (2012)
  • Author(s): 升田明孝, 苅山真美, 稲井 誠, 浅川倫宏, 濱島義隆, 菅 敏幸
  • Organizer: 日本薬学会132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] レモノマイシンの合成におけるアミノ糖の合成及びその導入 (2012)
  • Author(s): 長坂洋祐, 吉田篤史, 赤岩路則, 浅川倫宏, 濱島義隆, 横島 聡, 福山 透, 菅 敏幸
  • Organizer: 日本薬学会132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] (-)-レモノマイシンの合成研究 (2012)
  • Author(s): 吉田篤史, 赤岩路則, 横島 聡, 濱島義隆, 福山 透, 菅 敏幸
  • Organizer: 日本薬学会132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] TAN1251 の合成研究 (2011)
  • Author(s): 升田明孝, 浅川倫宏, 濱島義隆, 菅 敏幸
  • Organizer: 日本薬学会東海支部合同学術2011
  • Place of Presentation: 愛知
  • Year and Date: 2011-11-23