Transformation of Serine to Cysteine. β-Elimination Reactions in Serine Derivatives

O-Tosylated and O-diphenylphosphorylated serine derivatives undergo a β-elimination reaction on being treated with 0.1 N alkali or diethylamine in non-polar solvents, resulting in the formation of dehydroalanine derivatives. N-Carbobenzoxy-O-tosyl-l-serine methyl ester is converted to N-carbobenzoxy-S-trityl-dl-cysteine by reaction with tritylthiocarbinol sodium salt, followed by saponification. It has been observed that N-acyl-S-alkyl-l-cysteine esters are extensively racemized by saponification with alcoholic alkali, but little or no racemization is produced by alkali in 50% aqueous methanol or aqueous dioxane. © 1963, American Chemical Society. All rights reserved

A New Synthesis of Oxytocin Using S-Acyl Cysteines as Intermediates

The fully S,N-protected derivatives (VI-IX) of the nonapeptide amide, L-cysteinyl-L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl-L-cysteinyl-L-prolyl-L-leucylglycinamide, have been prepared by a step-by-step synthesis, using new N-protecting groups (the t-butyloxycarbonyl and the o-nitrophenylsulfenyl groups) in addition to the classical carbobenzoxy and new S-protecting groups (the S-benzoyl and S-carbobenzoxy groups). The selective removal of the S-protecting groups from compounds VI-IX by methanolysis afforded the N-protected oxytoceines (X-XII). Oxidation of the free thiol groups of X and XII by 1,2-diiodoethane led to the formation of N-carbo-benzoxy- (XIII), and N-t-butyloxycarbonyl-oxytocin, (XIV), respectively. The peptide obtained after decarbo-benzoxylation of the N-carbobenzoxy-oxytocin (XIII) was purified by countercurrent distribution and partition chromatography on Sephadex. The isolated material exhibited the chemical, physical, and biological activities of oxytocin. © 1966, American Chemical Society. All rights reserved

On cysteine and cystine peptides. Part VI. S-acylcysteines in peptide synthesis

S-p-Methoxybenzyloxycarbonyl-L-cysteine (pMZ-Cys) (I), as its N-o-nitrophenylsulphenyl derivative (II), can be used as an intermediate for the incorporation of cysteine residues in peptide synthesis. The pMZ group can be removed either by methanolysis or by treatment with hydrogen halides in acetic acid

On Cysteine and Cystine Peptides. I. New S-Protecting Groups for Cysteine

The problem of the synthesis of unsymmetrical cystine peptides with two or more cystine-S-S-bridges is discussed. For a solution of this problem, the following requirements must be fulfilled: (a) cysteines bearing different S-protecting groups selectively removable must be available and (b) procedures must be worked out for preventing the rearrangement of cystine chains during synthesis until their final incorporation in a multimembered ring system. Concerning the first of the above requirements, S-diphenylmethyl-L-cysteine (I) and S-trityl-L-cysteine (II) are proposed as the most suitable S-protected cysteines for the incorporation of cysteine residues in a peptide chain. The S-trityl group can be easily split off with heavy metal salts at room temperature, whereas the removal of the S-dipheuylmethyl group is also easily effected by the action of trifluoroacetic acid. The SH-groups thus liberated can be oxidized to the corresponding -S-S-derivatives. Several peptides of cysteine and cystine have been synthesized in this way. © 1962, American Chemical Society. All rights reserved

Transformation of L-Serine Peptides to L-Cysteine Peptides

The serine moieties of the peptides N-carbobenzoxy-L-serylglycine ethyl ester and N-carbobenzoxyglycyl-L-serylglycine ethyl ester were O-tosylated to give the corresponding O-tosyl derivatives IV and VI, respectively. Displacement of the O-tosyl groups of IV and VI by thiobenzoate anion afforded in excellent yields N-carbobenzoxy-S-benzoyl-L-cysteinylglycine ethyl ester (Va) and N-carbobenzoxyglycyl-S-benzoyl-L-cysteinyl-glycine ethyl ester (VIIa), respectively. A similar displacement by thioacetate anion afforded N-carbo-@r@nbenzoxy-S-acetyl-L-cysteinylglycine ethyl ester (Vb) and N-carbobenzoxyglycyl-S-acetyl-L-cysteinylglycine ethyl ester (VIlb). © 1965, American Chemical Society. All rights reserved

Nω -linked arginine peptides

From Nα-trityl-L-arginine benzyl ester, Nω-glycyl-, Nω-L-valyl-, and Nω-L-arginyl-L-arginine have been prepared. These non-typical arginine peptides were transformed, especially in alkaline solution, into ornithine and the corresponding 2-iminoimidazolidin-4-one (glycocyamidine) derivatives. In this way the suggestion of Zervas and Bergmann that a non-typical Nω-L-arginyl-L-arginine is formed as an intermediate in the disproportionation of arginine methyl ester was confirmed. When arginine derivatives are used in peptide synthesis, the formation of non-typical arginine peptides can occur. This could lead to the final incorporation of ornithine instead of arginine into the peptide chain. © Royal Society of Chemistry