Kinetics of intramolecular acyl migration of 1beta-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acids

Biol Pharm Bull. 2001 Jul;24(7):852-5. doi: 10.1248/bpb.24.852.

Abstract

The stereoselective acyl migration of diastereomeric 1beta-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acid [(R)-1PG and (S)-IPG, respectively] in phosphate buffer (pH 7.4) at 310K 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 1beta-O-isomer to the 2-O-acyl isomer (k12) was about one order magnitude larger than that for hydrolysis from 1beta-O-acyl isomer to aglycone (k10). The k12 of (R)-IPG (0.377 +/- 0.005 h(-1)) was about two times larger than that of (S)-IPG (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)-IPG (101.60kJ/mol), suggesting that (R)-IPG showed thermodynamically higher reactivity in acyl migration than (S)-1PG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Calibration
  • Chromatography, High Pressure Liquid
  • Glucuronides / chemistry*
  • Kinetics
  • Phenylpropionates / chemistry*
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism
  • Temperature

Substances

  • Glucuronides
  • Phenylpropionates