Synthesis and pharmacology of the potent angiotensin-converting enzyme inhibitor N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanyl-(S)-pyroglutamic acid

Abstract
Structure 3a, a potent angiotensin-converting enzyme inhibitor, was prepared in five steps from L-(+)-.alpha.-amino-4-phenylbutyric acid by construction of the activated side-chain ester 16, displacement with L-pyroglutamate ester anion, and deblocking. Diastereomer separation was accomplished by chromatography at the diester stage, 17. Pharmacological assays established that 3a parallels enalapril in its ability to inhibit converting enzyme and lower blood pressure.