Irreversible inhibition of zinc-containing protease by oxazolidinone derivatives. Novel inactivation chemistry

α-Benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (BOOA) having (αR,4S) and (αS,4R) configuration were designed and synthesized as a novel type of mechanism-based inactivators for carboxypeptidase A (CPA), and kinetic analysis demonstrated that they indeed inhibit the enzyme in a time-dependent manner with the second order inhibitory rate constants (kinact/KI) of 1.52 and 1.39 M−1 s−1 for (αS,4R)-BOOA and (αR,4S)-BOOA, respectively.