Carboxyalkyl peptide inhibitors of kininase II: chiral synthesis.
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.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004656:Enalapril / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015773:Enalaprilat; D007202:Indicators and Reagents; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D007202:Indicators and Reagents; D004656:Enalapril; D002216:Captopril; D015773:Enalaprilat