Propioxatins A and B, new enkephalinase B inhibitors. III. Total synthesis of propioxatin A

Propioxatin A, a potent enkephalinase B inhibitor produced by Kitasatosporia setae SANK 60684, was synthesized. The synthetic route involved a regio-selective synthesis of O-benzyl-alpha-propylsuccinic acid monohydroxamic acid via the acid chloride of alpha-propylsuccinic acid. The stereoisomer of the N-acyl moiety of natural propioxatin A was analyzed by X-ray crystallography in the form of the di-O-benzyl ester and was determined as S. Devalyl propioxatin A synthesized by the same method showed a higher Ki value for enkephalinase B than propioxatin A.