A Novel Method for Stereoselective Glucuronidation

A variety of hydroxylic aglycones can be glucuronidated directly with methyl 2,3, 4-tri-O-acetylglucopyranuronate (4a), activated with trimethylsilyl trifluoromethanesulfonate (Me₃Si-OTf). This reaction provides mostly β, and sometimes α, glucopyranosiduronic acid derivatives (referred to as glucuronides) rapidly and at low temperatures. The epimeric ratio depends on the relative aglycone nucleophilicity vs. its tendency to form a stabilized carbocation by the formal loss of-OH. Glucuronides of various aromatic and aliphatic aglycones as well as those of a number of cyanohydrins were prepared. The characteristic features of the ¹H NMR spectra of α and β derivatives which are presented are useful in the assignment of product stereochemistry and determination of epimeric ratios in those reactions where mixtures are obtained.