John F. Carson

Preparation of γ-glutamyl dipeptides of sulphur-containing amino-acids

γ-L-Glutamyl-L-methionine, -S-methyl-, S-propyl-, -S-allyl-, and -S-benzyl-L-cysteine were prepared by condensation of α-ethyl N-trifluoroacetyl-L-glutamate dicyclohexylammonium salt with the corresponding amino-acid ethyl ester hydrochloride followed by alkaline hydrolysis of the intermediate N-trifluoroacetyl dipeptide diethyl esters. The peptides containing S-substituted cysteine were difficult to crystallize but were more easily obtained as the crystalline ammonium salts.

Cyclization of (+)- and (-)-S-(2-methylprop-1-enyl)-L-cysteine S-oxides.

S-(2-Methylprop-1-enyl)-L-cysteine (5) has been oxidized to two sulphoxides (7a), [α]D25+128°, and (7b), [α]D25–84.3°(in H2O). Cyclization in base was stereospecific. The (+)-sulphoxide (7a) yielded the axial sulphoxide, (1S,3R)-5,5-dimethyltetrahydro-1,4-thiazine-3-carboxylic acid S-oxide (9), and the (–)-sulphoxide (7b) yielded the corresponding equatorial (1R) sulphoxide (10). This establishes the absolute configurations of the acyclic sulphoxides (7a and b) as R and S, respectively, at sulphur. Reduction of the cyclic sulphoxides to the corresponding cyclic sulphide, and reoxidation of this compound gave exclusively the equatorial sulphoxide (10), suggesting a large steric effect of the axial methyl group. Assignments of ring conformations and sulphoxide configurations are based on spectroscopic evidence.

Synthesis of the diastereoisomers of S-(2-carboxypropyl)-L-cysteine and their S-mono- and SS-di-oxides.

Addition of L-cysteine to methacrylamide followed by fractional crystallization yielded (+)- and (–)-S-(2-carbamoylpropyl)-L-cysteine, acidic hydrolysis of which gave the corresponding acids. These were converted into the corresponding two N-2,4-dinitrophenyl derivatives, two SS-dioxides, and four S-mono-oxtdes.