Cysteine derivatives with reactive groups as potential antitumor agents

Abstract

Cysteine derivatives having diazo ketone and chloro ketone functions have been prepared. In order to effect adequate protection for modifying the carboxyl group, cysteine was converted to a thiazolidine derivative I, which was then converted to the N-acetyl derivative VII. The active ester method or activation with DCC yielded the diazo ketone derivative VIII. Similar treatment of the parent compound I with DCC led to a self-condensation reaction giving a diketopiperazine VI. The diazo ketone derivative VIII has been used in preparing alpha-chloro ketone derivative X and a homologue of cysteine. Deblocking N-acetylated thiazolidine derivatives with various reagents did not proceed satisfactorily. Interaction of the N-acetylated blocked ester XII with trifluoroacetic acid opened the thiazolidine ring to give the N-acetylated blocked diester XIII and other products. The chloro ketone derivative X was found to have a moderate inhibitory activity against mouse mammary adenocarcinoma in cell culture. S-(1-Adamantyl)-L-cysteine was prepared and was found to be inactive.