Solid-Phase Synthesis of Enteropeptin A Analogues

Abstract Enteropeptin A is a sactipeptide natural product featuring a unique six-membered thiomorpholine core. Herein, we describe a solid-phase peptide synthesis (SPPS)-compatible approach to enteropeptin A analogues featuring a simplified sactionine motif. The strategy employs a readily accessible building block and efficient on-resin assembly. A “N to C” variant, differing in the directionality of the sactionine linkage was also readily accessible. Collectively, this work accelerates access to analogues of this important class of natural products.