Solid-Phase Total Synthesis of Biologically Active Cyclodepsipeptide Spiruchostatin A

Abstract

Cyclic peptides have been emerged as novel candidates for recent drug discovery, because cyclization or introduction of unnatural amino acid residues significantly improve physicochemical properties such as metabolic stability and cell permeability. Toward elucidation of the mode of action of cyclic peptides, we intensely investigated the structure-activity relationships study based on the total synthesis of naturally occurring cyclic peptides and its analogues utilizing solid-phase. Herein, we describe the details of total synthesis of spiruchostatin A, a potent histone deacetylase inhibitor, using a macrolactonization on the silyl-linked polymer-support.