再颁专利
USRE39151E1 Process for the preparation and purification of thiol-containing maytansinoids
有权
用于制备和纯化含硫醇的美登木素生物碱的方法
- 专利标题： Process for the preparation and purification of thiol-containing maytansinoids
- 专利标题（中）： 用于制备和纯化含硫醇的美登木素生物碱的方法
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申请号： US10410143申请日： 2003-04-10
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公开(公告)号： USRE39151E1公开(公告)日： 2006-06-27
- 发明人: Ravi Vankeepuram Jagannatha Chari , Wayne Charles Widdison
- 申请人： Ravi Vankeepuram Jagannatha Chari , Wayne Charles Widdison
- 申请人地址： US MA Cambridge
- 专利权人： Immunogen, Inc.
- 当前专利权人： Immunogen, Inc.
- 当前专利权人地址： US MA Cambridge
- 代理机构： Sughrue Mion, PLLC
- 主分类号： C07D491/12
- IPC分类号： C07D491/12 ; C07D498/06
摘要：
The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl (OMe)3H), lithium triethoxyaluminum hydride (LiAl(OEt)3H), lithium tripropoxyaluminum hydride (LiAl (OPr)3H), sodium trimethoxyaluminum hydride (NaAl (OMe)3H), sodium triethoxyaluminum hydride (NaAl(OEt)3H) and sodium tripropoxyaluminum hydride (NaAl(OPr)3H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (5) purifying the thiol-containing maytansinoid.
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