发明授权
- 专利标题: Use of catalytic antibodies for synthesizing epothilone
- 专利标题(中): 使用催化抗体合成埃坡霉素
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申请号: US09415453申请日: 1999-10-08
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公开(公告)号: US06294374B1公开(公告)日: 2001-09-25
- 发明人: Subhash C. Sinha , Richard A. Lerner , Carlos F. Barbas, III
- 申请人: Subhash C. Sinha , Richard A. Lerner , Carlos F. Barbas, III
- 主分类号: C12S1300
- IPC分类号: C12S1300
摘要:
Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.
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