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Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach.

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 ?-elimination reactions was also examined.

SUBMITTER: Li LS

PROVIDER: S-EPMC2768327 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach.

Li Lian-Sheng LS Sinha Subhash C SC

Tetrahedron letters 20090601 24

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 retr ...[more]

PMID: 20160897

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