METHODOLOGY FOR THE PREPARATION OF N-GUANIDINO-MODIFIED ARGININES AND RELATED DERIVATIVES

Methods for the preparation of N(G)-modified arginines and N(delta)-heterocyclic ornithines are described. The reactive cyanamide intermediate tert-butyl N(alpha)-Boc-N(delta)-cyano-L-ornithinate (2). prepared either by treatment of tert-butyl N(alpha)-BOC-L-ornithinate (5) with cyanogen bromide or by dehydration of tert-butyl N(alpha)-Boc-L-citrullinate (6), was utilized to prepare N(G)-hydroxy-L-arginine, N(G)-amino-L-arginine, and N(G)-methoxy-L-arginine. Intermediates 3a and 3b, derived from treatment of 5 with diphenyl cyanocarbonimidate (19), reacted with nitrogen nucleophiles to produce novel N(G)-cyano-L-arginine and N(delta)-heterocyclic L-ornithine analogs.