Synthesis and cytotoxicity of natural (+)-duocarmycin A and its three possible stereoisomers

Abstract

The title synthesis was accomplished by featuring 1) novel methoxycarbonylation of the C-4 position of the 5-aminoindoline (dl-13) by way of the isatin (dl-15), 2) the Dieckmann cyclization of diester (dl-19) to the methyl 2-methylindoxyl-2-carboxylates (dl-20 and dl-21), 3) the Wierenga-Kelly-Winstein Ar-3′ cyclization as key steps and by employing optical resolutions of various key synthetic intermediates (dl-26, dl-28, dl-34, and dl-36). In vitro cytotoxicity assay of the produced title compounds obviously disclosed that their cytotoxicity is closely related to absolute stereochemistries of cyclopropane moieties. © 1994 IUPAC