Preparation and Disulfide Interchange Reactions of Unsymmetrical Open-chain Derivatives of Cystine

Preparation of mono-(carbobenzoxyglycyl)-L-cystine was achieved by treatment of an excess of L-cystine in aqueous alkali with carbobenzoxyglycyl chloride. Decarbobenzoxylation of the compound by the action of hydrogen bromide in glacial acetic acid permitted the subsequent isolation of pure, crystalline monoglycyl-L-cystine. The bis-methyl, bis-benzyl, monomethyl and monobenzyl ester derivatives of monocarbobenzoxy-L-cystine were prepared by the usual esterification procedures. Conversion of the first-mentioned derivative to Nα-carbobenzoxy-Nα'-trityl-L-cystine bis-methyl ester was effected by the action of trityl chloride in chloroform containing triethylamine. Treatment of such product with hydrazine did not lead to the expected α-monohydrazide but rather induced a rapid disulfide interchange with the formation of the symmetrical bis-trityl-L-cystine bis-methyl ester and bis-carbobenzoxy-L-cystine bis-hydrazide as the only isolable products. Comparable disulfide interchange of this same compound as well as of monocarbobenzoxy- and monoglycyl-L-cystine was catalyzed by alkali in both aqueous and methanolic solution. The rate and extent of such interchange in basic solution was shown to increase with an increase in pH. © 1959, American Chemical Society. All rights reserved.