阅读说明：本技术 制备含硫醇或二硫化物的美登素酯及其中间体的非对映选择性方法 (Diastereoselective process for preparing thiol-or disulfide-containing maytansinoids and intermediates thereof ) 是由 G·丰塔纳 R·贝雷塔 M·塔迪 S·普林西奥托 于 2020-04-09 设计创作，主要内容包括：本发明公开了制备含硫醇或二硫化物基团的式(I)美登素酯的方法,其中R～(1)、R～(4)和R～(5)以及星号如说明书中的定义,通过使美登醇与对映体纯α-叠氮酸反应,随后使叠氮基还原,并使所得氨基酯与式(IX)化合物反应,(IX)R～(3)-S-S-X-COOH,其中,X和R～(3)如说明书中所定义,或与其反应性衍生物反应,并任选地还原所获得的含有二硫化物的美登素酯以得到美登素酯,其中R～(1)为-X-SH基团。(The invention discloses a process for the preparation of maytansinoids of formula (I) containing a thiol or disulfide group, wherein R is 1 、R 4 And R 5 And the asterisks are as defined in the specification, by reacting maytansinol with enantiomerically pure alpha-azido acid, followed by reduction of the azido group and reaction of the resulting amino ester with a compound of formula (IX), (IX) R 3 -S-S-X-COOH, wherein X and R 3 As defined in the description, or with reactive derivatives thereof, and optionally reducing the obtained disulfide containing maytansinoid ester to obtain a maytansinoid ester, wherein R is 1 Is a-X-SH group.)