1986 Fiscal Year Final Research Report Summary
Studies on the Development of Efficient Synthetic Routes to Non-classical <beta> -Lactam Antibiotics
| Project/Area Number |
59870073
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Institute of Medicinal Chemistry, Hoshi University |
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Principal Investigator |
KAMETANI Tetsuji Hoshi University ・ President, 薬学部, 教授 (80004521)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Makoto Daiichi Pharmaceutical Co. Ltd., Chief Researcher, 中央研究所, 主任研究員
FURUKAWA Minoru Daiichi Pharmaceutical Co. Ltd., Group Leader, 中央研究所, グループ長
TSUBUKI Masayoshi Hoshi University ・ Research Associate, 薬学部, 助手 (90163865)
HONDA Toshio Hoshi University ・ Associate Professor, 薬学部, 助教授 (70089788)
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| Project Period (FY) |
1984 – 1986
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| Keywords | carbapenem antibiotic / penem antibiotic / non-classical <beta> -lactam / 1,3-dipolar cycloaddition reaction / カルベノイド |
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| Research Abstract |
Development of efficient synthetic routes to carbapenem and penem antibiotics was achieved. 4-Acetyl-3-hydroxyethylazetidin-2-one, a common starting material for the synthesis of a carbapenem antibiotic thienamycin and for penem antibiotics were synthesized in an optically active form by using 1,3-dipolar cycloaddition reaction of benzyl crotonate and a chiral nitrone as a key step. Since this reaction was found to proceed stereoselectively and to be effective to construct a 3-hydroxyethyl side chain on <beta> -lactam ring, this was further utilized in the synthesis of thienamycin. 1,3-Dipolar cycloaddition of the chiral nitrone derived from diethyl diethyl acetonedicarboxylate with benzyl crotonate afforded the isoxazolidine whose reductive ring cleavage, followed by recyclization gave the important azetidinone which was finally converted into thienamycin.
Furthermore 6-aminopenicillanic acid derivatives were transformed into seco-penicillins by treatment with a carbenoid species. Conversion of the products into penem derivative or cephem derivative was also achieved by manipulation of the substituents on the <beta> -lactam ring.
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