A Highly Stereoselective Construction of β-Glycosyl Linkages by Reductive Cleavage of Cyclic Sugar Ortho Esters

The preparation of β-glycosides by the reductive cleavage of spiro sugar ortho esters is described in this report. This procedure is based on a concept completely different from those of other methods for glycosylation. Twelve sugar ortho esters that commonly possess perhydrospiro[2H-pyran-2,2‘-pyrano[3,2-d][1,3]dioxin] ring systems in their molecules were reduced by LiAlH4/AlCl3 or NaCNBH3/AlCl3. Among these ortho esters, those (9a−12a) prepared from the d-sugar lactones (1−4) and 2,3-di-O-benzyl-α-d-glucopyranoside (7) or those (19a, 20a) prepared from the l-sugar lactones (5, 6) and 2,3-di-O-benzyl-α-d-galactopyranoside (8) were selectively converted into β-(1 → 4)-glycosides (9b−12b or 19b, 20b) in excellent yields by the treatment of LiAlH4/AlCl3. In contrast, the ortho esters (13a−16a or 17a, 18a) that were prepared from combinations of the d-sugar lactones and 8 or those of the l-sugar lactones and 7 were efficiently reduced with NaBH3CN/AlCl3 to afford β-(1 → 6)-glycosides (13b−16b or 17b, 18b) selectively. It was remarkable that the resulting disaccharides were obtained with extremely high β-selectivity even in the cases with mannosyl or rhamnosyl glycosides. Moreover, these products would be useful units for the construction of branched saccharides, because the newly formed hydroxy groups could be again glycosylated without further deprotection procedures. The high regio- and stereoselectivity was totally explained by considering the structures and the conformations of these ortho ester molecules and the stereoelectoronic effects of their spiro ring systems. In addition, the preparation of the sugar ortho esters with glucosamine derivatives and the reactivity of these ortho esters are described in this report. N-Phthaloyl glucosamine derivatives (21, 22) were efficiently reacted with the benzyl-protected gluconolactone (1) in the presence of TMSOMe and TMSOTf to afford ortho esters (23a−c). After the conversion of the phthalimido functionality to the dibenzyl amino group, glucosylideneglucosamine (25) was reduced with LiAlH4/AlCl3 to afford β-(1 → 4)-glycoside (26) selectively.