发明名称 |
VERFAHREN UND VERWENDBARE ZWISCHENPRODUKTE FÜR PACLITAXEL SYNTHESE VON C-7,C-10 DI-CBZ BACCATIN III |
摘要 |
<p>The present invention relates to a method of producing paclitaxel or a paclitaxel analog comprising the esterification of C-7, C-10 di-CBZ 10-deacetylbaccatin III with an N-carbamate protected, C-2-protected 3-phenyl isoserine side chain. The C-7, C-10 carbobenzyloxy groups are then replaced with hydrogen and an acyl group is substituted at the C-3' nitrogen. The resulting compound is acylated at the C-10 hydroxyl position, and deprotected at the C-2' position by replacing the hydroxyl protecting group with hydrogen to produce paclitaxel or a paclitaxel analog. The present invention also relates to alternative methods of acylating a 10-hydroxy paclitaxel analog. The first method comprises dissolving a 10-hydroxy paclitaxel analog in an acceptable ether solvent therefor to form a first solution at a first temperature. The first solution is then cooled to a second temperature, and an alkali base is added to form an intermediate compound having a metal alkoxide at the C-10 position thereof, after which an acylating ageht is then added. The second method comprises dissolving a 10-hydroxy paclitaxel analog in an acceptable ether solvent therefor. An alkali salt is added, and a trialkyl amine base or pyridine is next added, followed by the addition of an acylating agent. The present invention is additionally directed to a C-10 metal alkoxide chemical intermediate for use in producing paclitaxel or paclitaxel analogs.</p> |
申请公布号 |
DE69918300(T2) |
申请公布日期 |
2005.06.30 |
申请号 |
DE1999618300T |
申请日期 |
1999.04.29 |
申请人 |
NAPRO BIOTHERAPEUTICS, INC. |
发明人 |
SISTI, J.;BRINKMAN, R.;MCCHESNEY, D.;CHANDER, C.;LIANG, XIAN;ZYGMUNT, JAN |
分类号 |
C07D305/14;(IPC1-7):C07D305/14 |
主分类号 |
C07D305/14 |
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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