Acid-catalyzed hydrolysis of (R)-4-[(1-methyl-3-oxo-1-butenyl) amino]-3-isoxazolidinone, a prodrug of cycloserine

Abstract

Hydrolysis of (R)-4-[(1-methyl-3-oxo-butenyl)amino]-3-isoxazolidinone(I), a prodrug of d-cycloserine, to (R)-4-amino-3-isoxazolidinone ( d-cycloserine) and 2,4-pentandione is general acid-catalyzed by carboxylic acids. Rectangular hyperbolic plots of pseudo first-order rate constants vs total carboxylic acid buffer concentrations suggest a change in the rate-determining step, from protonation of I at low acid concentrations to hydrolysis of protonated I at high carboxylic acid concentrations.