S-p-methylbenzyl-β-phenylcysteine: a potential tool for probing receptor topologies

Abstract

erythro and threo N-Acetyl-S-p-methylbenzyl-β-phenyl-DL-cysteine methyl esters were obtained by addition of p-methyltoluene-α-thiol to 4-benzylidene-2-methyloxazol-5-one in methanol–tetrahydrofuran under basic conditions. The diastereoisomers were separated as their methyl esters by fractional crystallization and the relative configuration assigned by X-ray crystallography. Both diastereoisomers were converted into their N-trifluoroacetyl derivatives and resolved using Carboxypeptidase A. Hydrazinolysis of the unchanged N-trifluoroacetyl amino acids gave the other enantiomers of the free amino-acids. Optical purity was determined using Eu(hfc)₃ chemical shift reagent on N-trifluoroacetyl-D-amino acid methyl ester by both ¹H and ¹⁹F NMR spectra. We discuss the conformation of this unique amino acid based on X-ray data and molecular mechanics calculations. Its usefulness in probing the opiate receptor site is also demonstrated.