Synthesis of sequential polydepsipeptides utilizing a new approach for the synthesis of depsipeptides

Sequential polydepsipeptides were synthesized by the depsipeptide active ester method using a new approach for the direct synthesis of N‐protected depsipeptide free acids from hydroxy acids. The method uses synthesis of Boc‐didepsipeptides by reaction of free hydroxy acids with Boc‐amino acid N‐hydroxysuccinimide esters catalyzed by 4‐dimethylaminopyridine and chain elongation of the free depsipeptides by the reaction with Boc‐amino acid N‐hydroxysuccinimide esters in an organic solvent system of acetonitrile‐tetrahydrofuran. The Boc‐depsipeptide free acids were activated as their N‐hydroxysuccinimide esters, which were polymerized after removal of the Boc‐protecting group. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004