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

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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 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 1β-O-isomer to the 2-O-acyl isomer(k_<12>)was about one order magnitude larger than that for hydrolysis from 1β-O-acyl isomer to aglycone(k_<10>). The k_<12> of(R)-1PG(0.377±0.005h^<-1>)was about two times larger than that of(S)-1PG(0.184±0.003h^<-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 310K for(R)-1PG(99.67kJ/mol)was smaller than that of(S)-1PG(101.60kJ/mol), suggesting that(R)-1PG showed thermodynamically higher reactivity in acyl migration than(S)-1PG.
公益社団法人日本薬学会の論文
2001-07-01