Carboxyalkyl peptide inhibitors of kininase II: chiral synthesis.

Abstract

Heretofore, carboxyalkyl peptide inhibitors of kininase II (e.g. N-[1-carboxy-3-phenylpropyl]-Ala-Pro, "enalaprilic acid") have been synthesized by means that yield racemic product. Typically, the secondary amine bond is formed by reacting an amino acid or dipeptide with a 2-keto carboxylic acid ester or imide. The group providing the 2-keto function must be used in excess, and the desired S,S,S isomer must be obtained by resolution procedures. We have developed a procedure whereby enalaprilic acid, RAC-X-64 and related compounds are synthesized stereospecifically and in relatively high yields.