Synthesis of 1-((S)-3-acetylthio-2-methylpropanoyl)-L-propyl-L-phenylalanine (alacepril) and one of its active metabolites, the desacetyl derivative (DU-1227).

Abstract
The synthesis of 1-((S)-3-acetylthio-2-methylpropanoyl)-L-phenylalanine 1 (alacepril, code name: DU-1219), a clinically used antihypertensive agent, and one of its active metabolites, 1-((S)-3-mercapto-2-methylpropanoyl)-L-prolyl-L-phenylalanine 2 (code name: DU-1227), is described. The application of chloral to the N-formylation of L-proline is also described. The presence of an intramolecular hydrogen bond in the trans conformer of 1 in solution is suggested on the basis of spectroscopic examinations of 1 and its ethyl ester 4.