Total Synthesis and Biosynthesis of Cyclodepsipeptide Cochinmicin I.

Phenylglycines are building blocks of many non-ribosomally synthesized peptides. The dihydroxyphenylglycine-containing cyclodepsipeptide cochinmicin I exhibits endothelin receptor antagonist activity. Therefore, it represents an interesting and synthetically challenging molecule because of the racemization-prone nature of dihydroxyphenylglycine. We present the total synthesis of cochinmicin I and the non-natural derivative cochinmicin VI and describe the identification and assignment of the cochinmicin ( cmn ) biosynthesis gene cluster, encoding a five-module non-ribosomal peptide synthetase for cochinmicin assembly.