ASYMMETRIC SYNTHESES OF PROTECTED DERIVATIVES OF CARNOSADINE AND ITS STEREOISOMERS AS CONFORMATIONALLY CONSTRAINED SURROGATES FOR ARGININE

All four stereoisomers of carnosadine were shown to be accessible from the lactone 1 or the diester 10 (or their enantiomers). Members of th e cis series (Z-cyclo-Arg') were obtained via a sequence involving ope ning lactone 1 with ammonia, Hofmann rearrangement, and incorporation of the guanidine group via an azide (3). The trans series (i.e. The E- cyclo-Arg' series) was prepared via a route which is similar, except t hat it begins with hydrolysis of the less hindered ester functionality of diester 10. Products from both series were manipulated into protec ted forms for peptide synthesis using the BOC or the FMOC approach.