Synthesis of the angiotensin converting enzyme inhibitor 3H-RAC-X-65

✍ Scribed by A. Y. K. Chung; J. W. Ryan; W. E. Groves; F. A. Valido; P. Berryer

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: French
• Weight: 349 KB
• Volume: 33
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580330606

✦ Synopsis

Abstract

We prepared the angiotensin converting enzyme (ACE) inhibitor N‐[1(S)‐carboxy‐3‐(4′‐^3^H)carboxanilidopropyl]‐L‐Ala‐L‐Pro (^3^H‐RAC‐X‐65). The triflate of D‐(+)‐lactic acid benzyl ester was reacted with N′‐(4‐iodophenyl)‐L‐glutamine methyl ester. The benzyl ester was removed with HF, and the free carboxyl group was coupled to L‐proline methyl ester via diphenylphosphorylazide. Methyl ester groups were removed by saponification. The product was dehalogenated in 10 Ci of ^3^H~2~ to yield ^3^H‐RAC at 24.3 Ci/mmole (89.7% yield). ^3^H‐RAC‐X‐65 was indistinguishable from its unlabeled counterpart in its ability to inhibit ACE and enter into a tightly bound enzyme:inhibitor complex.