A novel five-step synthesis of Boc-3,3-dimethylglutamic acid a-ethyl ester 11 is reported. All the steps are high yielding and simple to carry out. By use of the 3,3-dimethylglutamic acid building block, we successfully discovered a novel class of DPP-IV inhibitors, Glu-Pro-Nitrile dipeptide mimics 2, with high potency (IC50 < 40 nM). The consequence of 3,3-dimethyl substituent on the rate of intramolecular cyclization between N-terminal amine and 5-position amide bond in different buffer solutions was also evaluated.
Date:
2011-02
Relation:
Journal of the Chinese Chemical Society. 2011 Feb;58(1):108-117.
