Novel stereoselective sulfur ylide epoxidation reaction catalyzed by ferrocenylsulfide

A range of ferrocenyl sulfides are synthesized and screened. Among them 1-α-methysulphoferrocenyl ethyl acetate and 1-α-methysulphoferrocenyl alcohol are found to be unexpected catalysts, which is first reported mediating in sulfur ylide epoxidation reactions, furnishing a novel approach for highly stereoselective synthesis of oxiranes with 98%-100% trans-isomer. The protocol also has excellent yield, convenient workup and recycled starting material. The reason of high trars-selectivity is due to the bulky ferrocenyl sulfide group, which stabilizes the intermediates and determines the trans priority. A possible catalytic mechanism is also proposed.     

Stereoselective glucuronidation of carvedilol by Chinese liver microsomes

Objective: To study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes. Methods: The metabolites of CARV were identified by a hydrolysis reaction with β-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatogra-phy (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylisothiocyanate. Results: Two CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of Km and Vmax for (S)-CARV and (R)-CARV enantiomers were (118±44) μmol/L, (2 500±833) pmol/(min·mg protein) and (24±7) μmol/L, (953±399) pmol/(min·mg protein), respectively. Conclusion: These results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.