CHIRAL SYNTHESIS OF L-[C-14]PHENYLALANINE AND ITS INCORPORATION INTO THE RENIN INHIBITOR PD 132002

[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-C-14]Phenylalanine was synthesized in seven steps from (CO2)-C-14 in an overall yield of 33%. It was further converted to [C-14]PD 132002 in three more steps with an overall yield of 4.95%. The final specific activity was 35.5 mCi/mmol.