Synthesis and evaluation of ω-borono-α-amino acids as active-site probes of arginase and nitric oxide synthases

Enantiomerically pure omega-borono-alpha-amino acids of various chain lengths have been synthesized according to a general methodology involving condensation of alkenyl and alkynyl bromides with Ni-II complex of the Schiff base derived from glycine and (S)-2-[N'-(N-benzylprolyl)amino]benzophenone, hydroboration of the intermediate omega-unsaturated alpha-amino acids with diisopinocampheylborane, and oxidation with acetaldehyde. Some of these compounds act as potent inhibitors of rat liver and murine macrophage arginases, demonstrating that distance between the B(OH)(2) and alpha-amino acid groups is a key determinant for their interaction with arginase. In contrast, they are without effect on neuronal and inducible NO synthases.