Kinetics of Intramolecular Acyl Migration of 1β-O-Acyl Glucuronides of (R)- and (S)-2-Phenylpropionic Acids

Abstract

The stereoselective acyl migration of diastereomeric 1β-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acid [(R)-1PG and (S)-1PG, respectively] in phosphate buffer (pH 7.4) at 310 K was investigated using HPLC. The disappearance of (R)-1PG was faster than that of (S)-1PG according to pseudo first-order kinetics. A kinetic model describing the degradation reactions was constructed. The rate constant for acyl migration from the 1β-O-isomer to the 2-O-acyl isomer (k₁₂) was about one order magnitude larger than that for hydrolysis from 1β-O-acyl isomer to aglycone (k₁₀). The k₁₂ of (R)-1PG (0.377±0.005 h^-1) was about two times larger than that of (S)-1PG (0.184±0.003 h^-1). The results indicated that the stereoselectivity in the degradation of 1PG was apparently governed by the acyl migration from 1-isomer to 2-isomer. The kinetic parameters for acyl migration from 1-isomer to 2-isomer were estimated from temperature-dependent experiments using the transition state theory. The value of the free energy of activation at 310 K for (R)-1PG (99.67 kJ/mol) was smaller than that of (S)-1PG (101.60 kJ/mol), suggesting that (R)-1PG showed thermodynamically higher reactivity in acyl migration than (S)-1PG.