发明名称 |
PROCESS FOR THE PREPARATION AND PURIFICATION OF THIOL-CONTAINING MAYTANSINOIDS |
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 th e 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 (6) purifying the thiol-containing maytansinoid.
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申请公布号 |
CA2373554(A1) |
申请公布日期 |
2002.02.28 |
申请号 |
CA20012373554 |
申请日期 |
2001.04.26 |
申请人 |
IMMUNOGEN, INC. |
发明人 |
CHARI, RAVI VANKEEPURAM JAGANNATHA;WIDDISON, WAYNE CHARLES |
分类号 |
A61K31/5383;A61K47/48;A61P31/00;A61P31/12;A61P35/00;A61P37/06;A61P43/00;C07D498/18;(IPC1-7):C07D498/04 |
主分类号 |
A61K31/5383 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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