10-Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)-Dragmacidin D

Abstract

The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6″ position, which is consistent with other members of the dragmacidin family of natural products.