Enantioselective Total Syntheses of Vallesamidine and Schizozygane Alkaloids.

A general streamlined strategy for the enantioselective total syntheses of the schizozygane family of natural products and related alkaloid vallesamidine is described. Specifically, a catalytic enantioconvergent cross-coupling sets the quaternary stereogenic center in a pluripotent intermediate adorned with an olefin and three orthogonal carboxylate groups, upon which the modularity of the synthesis relies. A late-stage catalytic oxidative lactamization of an alkyne is instrumental in the first-generation synthesis of the schizozygane alkaloids. In the second-generation approach, a novel application of the van Leusen reaction for the generation of lactams is pivotal to accessing the schizozygane alkaloids from a common intermediate. The strategies outlined here are expected to enable detailed biological investigations as well as facilitate access to and provide solutions for the late-stage modification of bioactive alkaloids.