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