Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach
Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach
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DOI：
10.1016/j.tetlet.2009.03.205
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发表时间：
2009-06-17
影响因子：
1.8
通讯作者：
Sinha, Subhash C.
中科院分区：
文献类型：
--
作者：
Li, Lian-Sheng;Sinha, Subhash C.
采用闭环复分解方法制备了用于合成pro-1，2，9，9a-四氢环丙烯并[c]苯并[e]吲哚-4-酮四甲氧基吲哚甲酰胺（CBI-TMI）前药的三环前体。将三环中间体转化为CBI-TMI前药的高级前体，其配备有可能适用于使用醛缩酶催化抗体38 C2活化的接头。还检查了尝试的3SC 2催化的涉及逆羟醛和β-消除反应的羟基-pro-CBI中间体的两步活化。(C)2009爱思唯尔有限公司版权所有。
A tricyclic precursor for the synthesis of the prodrugs of pro-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indole-4-one tetramethoxyindolecarboxamide (CBI-TMI) was prepared using the ring-closing metathesis approach. The tricyclic intermediate was converted to an advanced precursor of a CBI-TMI prodrug equipped with a linker presumably suitable for activation using the aldolase catalytic antibody 38C2. An attempted 3SC2-catalyzed two-step activation of the hydroxy-pro-CBI intermediate involving retro-aldol and the beta-elimination reactions was also examined. (C) 2009 Elsevier Ltd. Ail rights reserved.