埃坡霉素A的氧化和还原转化

Oxidative and reductive transformations of epothilone A.

作者信息

Sefkow M, Kiffe M, Schummer D, Höfle G

机构信息

Gesellschaft für Biotechnologische Forschung mbH, Abt. Naturstoffchemie, Braunschweig, Germany.

出版信息

Bioorg Med Chem Lett. 1998 Nov 3;8(21):3025-30. doi: 10.1016/S0960-894X(98)00545-9.

DOI:10.1016/S0960-894X(98)00545-9

PMID:9873669

Abstract

The C7 hydroxy group of cytotoxic epothilone A was selectively oxidized using PDC. A selective oxidation of the C3 hydroxy group was accomplished with Me2S/(PhCO2)2 after in situ protection of C7-OH. Reduction of epothilone A or of a C5, C7 dioxo derivative with NaBH4 proceeded at the C5 carbonyl group. Oxidation and hydrogenation of the C16-C17 double bond proved to be difficult but it was easily cleaved with ozone and the resulting keto derivative was transformed to epothilone analogs with different side chains.

摘要

使用PDC对细胞毒性埃坡霉素A的C7羟基进行了选择性氧化。在对C7-OH进行原位保护后，用Me2S/(PhCO2)2实现了C3羟基的选择性氧化。用NaBH4还原埃坡霉素A或C5、C7二氧代衍生物时，反应发生在C5羰基上。事实证明，C16-C17双键的氧化和氢化很困难，但用臭氧很容易将其裂解，所得的酮衍生物被转化为具有不同侧链的埃坡霉素类似物。