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Chiral synthesis of L‐[ 14 C]phenylalanine and its incorporation into the renin inhibitor PD 132002
Author(s) -
Lee Helen T.,
Hicks James L.,
Johnson Donald R.
Publication year - 1991
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.2580290912
Subject(s) - chemistry , phenylalanine , yield (engineering) , renin inhibitor , stereochemistry , hydrazide , enantioselective synthesis , asymmetric carbon , alanine , peptide synthesis , chemical synthesis , amino acid , renin–angiotensin system , organic chemistry , catalysis , in vitro , biochemistry , medicine , materials science , optically active , blood pressure , metallurgy , radiology
[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.