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Synthesis of the angiotensin converting enzyme inhibitor 3 H‐RAC‐X‐65
Author(s) -
Chung A. Y. K.,
Ryan J. W.,
Groves W. E.,
Valido F. A.,
Berryer P.
Publication year - 1993
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580330606
Subject(s) - chemistry , saponification , enzyme , yield (engineering) , trifluoromethanesulfonate , stereochemistry , enzyme inhibitor , medicinal chemistry , organic chemistry , catalysis , materials science , metallurgy
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.