| Project/Area Number |
02403026
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
YONEMITSU Osamu Hokkaido University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60001038)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Noriyuki Hokkaido University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (40188959)
HORITA Kiyoshi Hokkaido University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (50181540)
NISHIDA Atsushi Hokkaido University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (80130029)
HAMADA Tatsuo Hokkaido University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40001979)
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| Project Period (FY) |
1990 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥32,100,000 (Direct Cost: ¥32,100,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1990: ¥22,100,000 (Direct Cost: ¥22,100,000)
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| Keywords | Macrolide antibiotic / Polyether antibiotic / Polyether macrolide / Asymmetric radical cyclization / Hetero Diels-Alder reaction / Sereoselective reaction / Computer chemistry / Conformational control / アグリコン / 立体制御 / NMR / 保護基 / ポリエ-テル抗生物質 / マクロリドポリエ-テル / 分子力場計算 |
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| Research Abstract |
The object of this research was to contribute to the progress of modern fine organic synthetic chemistry through the development of a new methodology for selective and efficient syntheses of very complex molecules such as macrolide and polyether antilbiotics and marine polyether-macrolides. During the past four years research the following five results were mainly obtained.
1. Synthsis of macrolides : Erythromolide A, the most important aglycon, was synthesized via an extremely efficient macrolactionization with the aid of MM2-CONFLEX3 calculation and NMR analysis of a seco-acid derivative, Carbonolide A, leuconolides, and maridonolides were also synthesized completely stereoselectively from carbonolide B through conformational control of 16-membered macro-rings.
2. Synthesis of polyethers : Highly stereoselective synthesis of complex isolasalocid A, lasalocid A, salinomycin, and lysocellin by a common methodology was completed.
3. Synthesis of polyether-macrolides : Stereoselective synthesis of four fragments of halichondrin B was completed, and coupling among the fragments is in progress.
4. Asymmetric radical cyclization : A new method for the synthesis of optically active five and six membered rings was developed via asymmtric radical cyclization between an acetylene and an alpha, beta-unsaturated ester in the presence of a Lewis acid.
5. Hetero Diels-Alder reaction : One-step synthesis of optically active dihydropyridine derivatives was developed via a hetero Diels-Alder reaction between tosylimines and diene derivatives. This method was successfully applied for the synthesis of a polyamine alkaloid, cannabisativine.
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