| Project/Area Number |
60570999
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
MAKI Yoshifumi Gifu Pharm. Univ., Faculty of Pharmacy, Prof., 薬学部, 教授 (00082959)
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| Co-Investigator(Kenkyū-buntansha) |
KITADE Yukio Gifu Pharm. Univ., Faculty of Pharmacy, Assistant, 薬学部, 助手 (20137061)
SAKO Magoichi Gifu Pharm. Univ., Faculty of Pharmacy, Assistant, 薬学部, 助手 (10137060)
HIROTA Kosaku Gifu Pharm. Univ., Faculty of Pharmacy, Associate Prof., 薬学部, 助教授 (90082982)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | <beta> -lactam antibiotics / transition-state analogs / regio-selective chemical modification / antibacterial activity / β-ラクタマーゼ阻害作用 |
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| Research Abstract |
One of the major problems in the chemotherapy by <beta> -lactam antibiotics is the increasing appearance of resistant bacteria.
The purpose of our research project is concerned in the synthesis of partially modified penicillins which are effective to the penicillin-resistant bacteria. The <beta> -lactam carbonyl group in the penam ring possesses chemical reactivities of the carbonyl groups rather than the amide carbonyl groups. Thus, the regio-selective modification of the <beta> -lactam carbonyl group of penicillins is possible by acting various reagents which are reactive to the carbonyl groups.
As a result of detailed study along this line, 7-exomethylenepenicillins (3A, R'=H) and (3B, R'=H) were prepared by the reaction of penicillin (4) with Wittig's reagents. The biological evaluation shows that the Z-isomer of (3B, R'=H) has a weak activity as the <beta> -lactamase inhibitor. Synthesis of transition-state analogs, i.e., 7-deoxopenicillin (1, R'=H) and spiro[oxirane-2,7'- penicillin] (2, R'=H), however, was not achieved because of instability of the reaction intermediates under the conditions employed.
During the course of the present studies, we found also facile preparative methods for alcohols (5) and S-ylides (12) which can be utilized as synthetic intermediates of some optically active substances.
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