| Project/Area Number |
09307051
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Okayama University of Science |
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Principal Investigator |
YONEMITSU Osamu Okayama University of Science, Faculty of Science, Professor, 理学部, 教授 (60001038)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Noriyuki Toyama Prefectural University, Biotechnologe Research Center, Associate Professor, 工学部・生物工学研究センター, 助教授 (40188959)
UENISHI Jnu-ichi Okayama University of Science, Faculty of Science, Professor, 理学部, 教授 (50167285)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | macrolide / stereoselective synthesis / lactonization / conformation / protecting group / computational chemistry / 不斉アルドール反応 / 立体選択的反応 / マクロライト |
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| Research Abstract |
The purpose of this research was to develop a new synthetic methodology of a series of complex natural macrolides through convenient and efficient syntheses of many fragments and their couplings, starting from inexpensive materials such as glucose. The following results were mainly obtained during the past three years research.
Recently, we developed two methods for the construction of macro-rings ; macrolactonization and Horner-Emmons cyclization of the corresponding seco-acids and aldehyde-ketophosphonates, respectively. This methodology, combined with computer-aided conformational analysis (using both molecular mechanics and molecular orbital calculations) and structural design of key intermediates, was now applied to synthetic studies of tedanolide, an antitumor marine macrolide. Two fragments, C1-C12 and C13-C23, were synthesized stereoselectively staring from methyl hydroxyisobutyrates and coupled to give a seco-acid, which converted efficiently to an 18-mombered lactone, a key intermediate for the synthesis of tedanolide. Stereoselective syntheses of new fragments, which will be converted to another seco-acid, the corresponding lactone, and tedanolide more reasonably, were also completed.
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