Synthetic study on pactamycin by means of desymmetrization
Project/Area Number |
19K05460
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 33020:Synthetic organic chemistry-related
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Research Institution | University of Shizuoka |
Principal Investigator |
Makoto Inai 静岡県立大学, 薬学部, 講師 (20621626)
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Co-Investigator(Kenkyū-buntansha) |
菅 敏幸 静岡県立大学, 薬学部, 教授 (10221904)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | パクタマイシン / 非対称化 / ロジウム触媒 / ヘテロDeals -Alder / ニトロソ化合物 / ニトロソDiels-Alder反応 |
Outline of Research at the Start |
「連続する含窒素・酸素四置換炭素」の高エナンチオ・ジアステレオ選択的な構築法の開発は,現在でも非常に挑戦的な研究課題であり,それらを応用した天然物の全合成や生物活性評価にも興味が持たれる.本研究課題では,これら合成法の開発を基盤とした天然物の骨格構築法を開発し,全合成及び生物活性評価への展開を目的とする. まず,非対称化反応を用いたパクタマイシン類のラセミ全合経路を確立する.さらに, 不斉非対称化を伴うアジリジン化反応及び [4+2] 環化付加反応を応用したパクタマイシン,パクタマイケートのエナンチオ選択的全合成を達成する.
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Outline of Final Research Achievements |
The aminocyclopentitol antibiotic pactamycin, isolated from fermentation broth of Streptomyces pactum var. pactum, exhibits antitumor and antiviral activities, as well as cytotoxicity toward Gram-positive and Gram-negative bacteria. The molecule contains six contiguous stereogenic centers with three consecutive tetra-substituted carbons on a heteroatom-rich cyclopentane core, and this novel structure, as well as the remarkable biological activities, makes it an attractive target for total synthesis. Our first-generation synthetic approach, the construction of the cyclopentane core of pactamycin achieved by catalytic Rh-mediated desymmetric aziridination and ring-contraction reaction as key steps. Our second-generation synthetic approach, A formal total synthesis of pactamycin accomplished by face-selective and regioselective nitroso Diels-Alder (NDA) reaction as key step in 11 steps and 20% yield.
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Academic Significance and Societal Importance of the Research Achievements |
「連続する含窒素・酸素四置換炭素」の高エナンチオ・ジアステレオ選択的な構築法の開発は,現在でも非常に挑戦的な研究課題であり,それらを応用した天然物の全合成や生物活性評価にも興味が持たれる.本研究課題では,これら合成法の開発を基盤とした天然物の骨格構築法を開発し,全合成及び生物活性評価への展開を実施し,代表的な連続含窒素天然物であるパクタマイシンの新たな主骨格構築法の開発,形式合成を達成した. 本研究課題にて確立した 2 つの含窒素連続不斉四置換炭素築法は,パクタマイシン類のみならず様々な天然物に応用可能な汎用性の高いもである.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] S-Adenosylhomocysteine Analogue of a Fairy Chemical, Imidazole-4-carboxamide, as its Metabolite in Rice and Yeast and Synthetic Investigations of Related Compounds2021
Author(s)
Hitoshi Ouchi , Takuya Namiki , Kenji Iwamoto , Nobuo Matsuzaki , Makoto Inai , Mihaya Kotajima , Jing Wu , Jae-Hoon Choi , Yoko Kimura , Hirofumi Hirai , Xiaonan Xie , Hirokazu Kawagishi , Toshiyuki Kan
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Journal Title
J Nat Prod .
Volume: 84
Issue: 2
Pages: 453-458
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Pactamycin and Its Derivatives: Improved Synthesis Route2020
Author(s)
Kohki Ohmi, Yusuke Miura, Yuta Nakao, Atsumi Goto, Satoshi Yoshimura, Hitoshi Ouchi, Makoto Inai, Tomohiro Asakawa, Fumihiko Yoshimura, Mitsuru Kondo, Toshiyuki Kan
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Journal Title
European Journal of Organic Chemistry
Volume: 2020
Issue: 4
Pages: 488-491
DOI
Related Report
Peer Reviewed
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[Journal Article] Concise Synthesis of TAN1251C2019
Author(s)
Nagasaka Y, Asakawa T, Shintaku S, Masuda A, Matsumura K, Inai M, Ishikawa Y, Egi M, Hamashima Y, Kan T.
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Journal Title
HETEROCYCLES
Volume: 99
Issue: 2
Pages: 1095-1116
DOI
Related Report
Peer Reviewed
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