关于用于抗体前药疗法的双炔酰菌素前药的研究。
Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach.
作者信息
Li Lian-Sheng, Sinha Subhash C
机构信息
The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.
出版信息
Tetrahedron Lett. 2009 Jun 1;50(24):2933-2935. doi: 10.1016/j.tetlet.2009.03.205.
Abstract
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 38C2-catalyzed two-step activation of the hydroxy-pro-CBI intermediate involving retro-aldol and the β-elimination reactions was also examined.
摘要
采用闭环复分解方法制备了一种用于合成前药1,2,9,9a-四氢环丙[c]苯并[e]吲哚-4-酮四甲氧基吲哚甲酰胺（CBI-TMI）的三环前体。将该三环中间体转化为CBI-TMI前药的高级前体，该前体带有一个可能适合使用醛缩酶催化抗体38C2进行活化的连接子。还研究了尝试通过38C2催化的涉及逆羟醛反应和β-消除反应的两步法对羟基前体CBI中间体进行活化。
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