Chiral synthesis of L-[14C]phenylalanine and its incorporation into the renin inhibitor PD 132002

✍ Scribed by Helen T. Lee; James L. Hicks; Donald R. Johnson

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 327 KB
• Volume: 29
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580290912

✦ Synopsis

Abstract

[1S‐(1R*,2S*,3R*)]‐3‐[[1‐(Cyclohexylmethyl)‐2,3‐dihydroxy‐5‐methylhexyl]‐amino]‐N‐[N‐(4‐morpholinosulfonyl)‐L‐ phenylalanyl]‐3‐oxo‐DL‐alanine methyl ester (PD 132002) was found to be a renin inhibitor and thus potentially useful for the treatment of hypertension. This peptidomimetic agent contains an L‐phenylalanine residue which was chosen as the site for carbon‐14 incorporation. The chiral synthesis using (4S)‐4‐(phenylmethyl)‐2‐oxazolidinone as a chiral auxiliary for asymmetric hydrazide formation was modified to make it amenable to carbon‐14 synthesis.

L‐[1‐^14^C]Phenylalanine was synthesized in seven steps from ^14^CO~2~ in an overall yield of 33%. It was further converted to [^14^C]PD 132002 in three more steps with an overall yield of 4.95%. The final specific activity was 35.5 mCi/mmol.