Chemistry of 4-deoxypentenosides and their application toward the synthesis of L-sugars

Gang Cheng

Abstract

4-Deoxypentenosides (4-DPs) are unsaturated pyranoside derivatives with structural homology to glycals, which can be epoxidized with high facioselectivity at low temperature by DMDO. The resulting 4-epoxypyranosides can undergo stereoselective additions at the C5 carbon, and are useful synthetic intermediates for rare or unnatural pyranosides. We investigate the ZnBr2 -mediated addition of carbon nucleophiles to 4α-epoxypyranosides for the synthesis of C5-substituted pyranosides with L-ido configuration. The nucleophilic ring opening proceeds with (complete) syn selectivity, and is particularly compatible with the addition of sp2 , sp , or allyl organozinc halides. This methodology was applied toward the synthesis of L-iduronic acid, a vital component of heparan sulfate, neosamine B, a 2,6-diaminopyranoside found in several aminoglycoside antibiotics. Systematic study on DMDO oxidation revealed that the epoxidation proceeded with anti -selectivity to two out of three substitutents at C1-C3, independent of their relative stereochemical relationship or electronic character. Density functional theory (DFT) calculations using a π-polarized frontier molecular orbital (PPFMO) model strongly suggested a stereoelectronic bias in the ground-state conformations of 4-DPs, which correlated well with the observed stereoselective outcomes. Finally, β-thiophenyl 4-deoxypentenoside was examined as a glycosyl donor for oligosaccharide synthesis. Glycosylation with β-D-glucose proceeded with exclusive α selectivity. Post-glycosylation modifications of unsaturated disaccharides, namely epoxidation and epoxide ring-opening reactions, could be achieved with high levels of seteroselectivity. This sets the stage for oligosaccharide synthesis based on post-glycosylation modifications.