紫杉醇半合成的工艺改进

Semi-synthesis of taxol by technological improvement

摘要:

以肉桂酸为原料，通过单过氧化硫酸氢钾复盐进行环氧化反应，再用溴苄保护，制得3-苯基缩水甘油酸苄酯，然后经Ritter反应，形成噁唑环的结构，再脱去酯基保护基、酸化，得到4,5-二氢-2,4-二苯基-1,3-噁唑-5-甲酸，后者再经过拆分即得到紫杉醇C-13侧链前体。将7-三乙基硅氧基巴卡亭 Ⅲ与此C-13侧链前体对接，然后脱TES保护基，酸化开环，即得紫杉醇。总收率为4.5%。部分中间体和目标产物的结构经1H-NMR，13C-NMR, MS进行了表征。

Abstract:

The C-13 side-chain precursor (4R,5S)-2,4-diphenyl-4,5-dihydroxazole-5- carboxylic acid was prepared from Cinnamic acid via epoxidation of C=C double bond with Oxone,benzyl protection, Ritter reaction, hydrolyzation, and resolution with (+)-Quinidine. Thus by linking it to 7-TES-Baccatin Ⅲ, taxol could be synthesized. The yield is 4.5% in the overall steps. Some intermediates and the target product were identified by means of 1H-NMR, 13C-NMR and MS.