1986 Fiscal Year Final Research Report Summary
Development of highly selective reactions and application to the synthesis of complex natural products.
| Project/Area Number |
59430023
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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 Pharmceutical Sciences, Professor, 薬学部, 教授 (60001038)
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| Co-Investigator(Kenkyū-buntansha) |
HORITA Kiyoshi Hokkaido University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (50181540)
HAMADA Tatsuo Hokkaido University, Faculty of Pharmaceutical Sciences, Associate Prof., 薬学部, 助教授 (40001979)
IKEDA Kazuyoshi Hokkaido University, Center for Instrumental Analysis, Associate Professor, 機器分析センター, 助教授 (20001042)
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| Project Period (FY) |
1984 – 1986
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| Keywords | Macrolide antibiotic / Polyether antibiotic / Sugar / Total synthesis / Stereoselective reaction / Stereocontrol / 保護基 |
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| Research Abstract |
Research programs on the synthesis of organic compounds with high value from readily available materials are now extremely important for the great future of our country having very poor natural resources. Development in the modern fine synthetic organic chemistry consisting of highly functional, regio, and stereoselective reactions helds the key to success in such programs.
Recently, we planned to synthesize some representative macrolide and polyether antibiotics from sugars, especially most readily available D-glucose, by a common synthetic methodology consisting mainly of 1) synthesis of three contiguous chiral centers by cyclic or acyclic stereocontrolled introduction of substituents at C-3 and C-5 positions of D-glucose, 2) construction of new chiral centers with at least 10 : 1 stereoselction by use of highly stereoselective reactions, 3) selective use of benzyl-type protecting groups for hydroxy groups (MPM, DMPM) removable by DDQ oxidation.
In our synthetic programs, the following results so far obtained. 1) Benzyl-type (Bn, MPM, DMPM) protecting groups selectively removable by DDQ oxidation or catalytic hydrogenolysis with Raney Ni were developed. 2) Stereoselective synthesis of substituted tetrahydrofurans and tetrahydropyrans by stereocontrolled acid-catalyzed cyclization. 3) Highly stereoselective synthesis of macrolide aglycons having complex structures such as methynolide, pikronolide, erythronolide A, and tylonolide from Dglucose as a chiral starting materials was completed. 4) Highly stereoselective synthesis of the polyether antibiotic salinomycin from D-glucose, D-mannitol, and L-lactic acid was achieved.
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