Li Lian-Sheng, Sinha Subhash C
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.
Tetrahedron Lett. 2009 Jun 1;50(24):2933-2935. doi: 10.1016/j.tetlet.2009.03.205.
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.
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。