DERIVATIVES AND PRECURSORS OF CAPTOPRIL AND ITS ANALOGUES AND METHODS FOR PREPARING CAPTOPRIL AND ITS ANALOGUES THEREFROM

摘要

This invention relates to novel methods forconverting a diastereomeric mixture of S-protectedderivatives of an orally active inhibitor of anangiotensin-converting enzyme (ACE) and its analogues intoits separate optically resolved diastereomeric components.Specifically the invention relates to methods for thepreparation of optically purified captopril for thepreparation of optically purified captopril and its analogsfrom racemic precursors. This resolution process isachieved through the fractional crystallization of S-protected derivatives of captopril and its precursors,which derivatives are useful for the reason that they are(1) easily prepared from novel precursors, (2) resolvableto their optically purified stereoisomeric species and (3)convertible to non-derivatized stereoisomeric species whichcorrespond to the pharmacologically active inhibitor andits analogues. The invention also pertains to theaforesaid novel derivatives utilized in the resolutionmethods and their precursors. In addition, novel methodsfor preparing the derivatives and their precursors are alsonoted herein.