| Project/Area Number |
63870088
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B).
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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, 助手 (40188959)
HORITA Kiyoshi Hokkaido University, Faculty of Pharmaceutical Sciences Instructor, 助手 (50181540)
NISHIDA Atsushi Hokkaido University, Faculty of Pharmaceutical Sciences Instructor, 助手 (80130029)
HAMADA Tatsuo Hokkaido University, Faculty of Pharmaceutical Sciences Associate Professor, 助教授 (40001979)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1990: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1989: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1988: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Macrolide antibiotic / Aglycon / Polyether antibiotic / Protecting group / Macro-lactonization / Conformational control / Molecular mechanics calculation / マクロラクトン閉環反応 / ウイテック・ホ-ナ-反応 / ポリエーテル抗生物質 / 立体選択的合成 / 分子内ウイテック・ホーナー反応 |
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| Research Abstract |
Macrolide and polyether antibiotics with multiple chiralty centers, owing to the presence of many substituents and functional groups, have received much recent synthetic attention because of their significant pharmacological and biological activities. The synthesis of such complex molecules makes sigumificant contributions to the progress of modern synthetic organic chemistry. For their syntheses new synthetic methodologies mainly consisting of means of stereochemical control in acyclic systems, selective use of suitable protecting groups, and efficient macro-cyclization are primarily required
. In this study, highly selective and efficient syntheses of some typical macro-lides and polyethers have been achieved. Erythronolide A, the most important and famous aglycon, was synthesized via a extremely efficient macrolactonization with the aid and NMR analysis of MMP2 calculation of a secoacid derivative. Leuconolides and maridonolides were also synthesized completely stereoselectively from carbonolide B, recently synthesized from D-glucose, etc., via conformational control of 16-membered macro-rings. A new stereoselective synthetic method of tetrahydrofurans based on chelation control under thermodynamic conditions was applied to the stereoselective synthesis of polyether antibiotics, lasalocid A and isolasalicid A.
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