Studies Toward the Total Synthesis and Stereochemical Assignment of Microspinosamide

Abstract

Efforts toward the total synthesis and stereochemical assignment of the cyclic depsipeptide natural product microspinosamide are described. A single diastereoisomer was targeted corresponding to the predicted structure of the natural product incorporating a (2S, 3R)-β-hydroxy-p-bromophenylalanine residue. Assembly was achieved through the initial synthesis of a cyclic depsipeptide and a linear peptide thioester fragment by solid-phase peptide synthesis, followed by fusion of the two fragments through a native chemical ligation–oxidation protocol. Extensive spectroscopic analysis showed structural differences to the isolated natural product, suggesting that a diastereoisomer of microspinosamide had been synthesised. This work lays the foundation for the future synthesis of the correct diastereoisomer.