Highly chemoselective oxidative dimerization of indolosesquiterpene alkaloids: a biomimetic approach to dixiamycin

Abstract

Dimeric indolosesquiterpene alkaloids, typically N–N- and C–N-linked xiamycin dimers, feature a pentacyclic framework with four contiguous stereogenic centers at the periphery of a trans-decalin scaffold to which a carbazole unit is attached. In comparison with actual biosynthetic dixiamycin derivatives, we designed C–C-linked xiamycin dimers, aiming to use them as a powerful tool to create unique scaffolds as drug candidates. In this work, we disclose the first synthetic route to access a C–C dimeric indolosesquiterpene skeleton, featuring a hypervalent iodine (PIFA)-catalyzed oxidative dimerization reaction in a single-step operation with overwhelming control over the chemoselectivity and regioselectivity. This strategy has been successfully applied to the synthesis of a C–C dimer of xiamycin A (3) and xiamycin A methyl ester (15) that demonstrates a new synthetic pathway for dimeric indolosesquiterpene alkaloids.