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

Abstract

Enantiomerically pure ω-borono-α-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 ω-unsaturated α-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 α-amino acid groups is a key determinant for their interaction with arginase. In contrast, they are without effect on neuronal and inducible NO synthases.