A NEW SYNTHESIS OF CARNOSINE, WITH SOME OBSERVATIONS ON THE SPLITTING OF THE BENZYL GROUP FROM CARBOBENZOXY DERIVATIVES AND FROM BENZYLTHIO ETHERS

Abstract

The question of the physiological origin and function of carnosine is particularly intriguing, since the compound contains not only the imidazole ring, which is highly suggestive of physiological activity, but contains as well the only p-amino acid known to exist in the body. Furthermore it occurs in muscle tissue in amounts greater t,han any other nitrogenous extractive with the exception of creatine. Yet practically nothing is known of its formation, its function, or its fate. The main reason for this lack of knowledge is, in our opinion, the relative inaccessibility of the compound. Its isolation from muscle tissue is a tedious process and the syntheses that have been devised have given exceedingly poor yields. It seemed to us that if the product were made more readily available, a greater variety of physiological studies might be undertaken and more thus learned of the intermediary metabolism and the physiological role of this interesting dipeptide. With this purpose in mind we undertook the synthesis of carnosine and have succeeded in working out a method by which the pure crystalline peptide can be obtained in a 65 per cent yield, based on the histidine used. This is considerably more than a lo-fold increase over that of previously reported syntheses. The constitution of this dipeptide, which was isolated by Gulewitsch and Amiradzibi (1) in 1900 from the extractives of muscle tissue, was shown by the work of Baumann and Ingvaldsen (2) and that of Barger and Tutin (3) in 1918 to be ,&alanyl-khistidine. In addition to assembling analytical proof for this structure both