Diastereoselectivity in the transglycosidation of methyl 2-deoxy-3,4,6-tri-O-methyl-2(N-methylacetamido)-d-glucopyranoside, -galactopyranoside, and -mannopyranoside with racemic 2-butanol under reductive-cleavage conditions

The fully methylated derivatives of methyl 2-acetamido-2-deoxy-β-d-glucopyranoside, methyl 2-acetamido-2-deoxy-β-d-galactopyranoside, and methyl 2-acetamido-2-deoxy-α-d-mannopyranoside were subjected to reductive-cleavage conditions in the presence of various promoters, and the rates of formation of the respective oxazolinium ions were established by 1H NMR spectroscopy. When oxazolinium ion formation was complete, racemic 2-butanol was added to each reaction, and the time-course for transglycosidation to form the respective 2-butyl glycosides was established by gas-liquid chromatography. These studies established the minimum times required for conversion of these acetamido sugars to their respective oxazolinium ions under various reductive-cleavage conditions and the minimum times required for their transglycosidation with 2-butanol. In separate experiments, oxazolinium ions having the gluco, galacto, and manno configuration were formed in the presence of trimethylsilyl trifluoromethanesulfonate as the promoter, then reacted with racemic 2-butanol either in the presence or absence of a proton acceptor (2,6-di-tert-butylpyridine), and the time-course for formation of the individual diastereomeric glycosides was established by gas-liquid chromatography. For all three oxazolinium ions, diastereoselectivity was observed in their conversion to the respective diastereomeric (R)- and (S)-2-butyl glycosides. When the transglycosidations were conducted in the absence of a proton acceptor, the kinetically preferred diastereomers were, in all three cases, present in the lowest proportion at equilibrium, whereas when the transglycosidations were conducted in the presence of a proton acceptor, the ratios of the diastereomers were constant throughout the reaction and the kinetically preferred diastereomers predominated. These experiments have established the ratios of the diastereomeric 2-butyl glycosides to be expected when the reductive-cleavage method is employed for the analysis of acetamido sugar-containing polysaccharides.