A straightforward synthesis and partial hydrolysis of cysteine-derived 2,5-diketopiperazines

A mild and straightforward preparation of cysteine-derived 2,5-diketopiperazines (DKPs) is reported, by cyclization of (R)-2,2-dimethyltetrahydrothiazole-4-carboxylic acid hydrochloride or of (R)-tetrahydrothiazole-4-carboxylic acid hydrochloride, mediated by HBTU and DIEA. One DKP has been characterized by X-ray analysis, while the other has been hydrolyzed to cyclo-Cys-Cys. The preparation of this latter compound has been previously reported to be troublesome and low yielding.