A highly stereoselective construction of beta-glycosyl linkages by reductive cleavage of cyclic sugar ortho esters

The preparation of beta -glycosides by the reductive cleavage of spiro suga r ortho eaters is described in this report. This procedure is based on a co ncept completely different from those of other methods for glycosylation. T welve 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-alpha -D-gluco pyranoside (7) or those (19a, 20a) prepared from the L-sugar lactones (5, 6 ) and 2,3-di-O-benzyl-alpha -D-galactopyranoside (8) were selectively conve rted into beta-(1 --> 4) glycosides (9b-12b or 19b, 20b) in excellent yield s 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 a nd 8 or those of the L-sugar lactones and 7 were efficiently reduced with N aBH3CN/AlCl3 to afford beta-(1 --> 6)-glycosides (13b-16b or 17b, 18b) sele ctively. It was remarkable that the-resulting disaccharides were obtained w ith extremely high beta -selectivity even in the cases with mannosyl or rha mnosyl glycosides. Moreover, these products would be useful units for the c onstruction of branched saccharides, because the newly formed hydroxy group s 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 ste reoelectoronic effects of their spiro ring systems. In addition, the prepar ation of the sugar ortho esters with: glucosamine derivatives and the react ivity of these. ortho esters are described in this report. N-Phthaloyl gluc osamine. derivatives (21, 22) were efficiently reacted with the benzyl-prot ected gluconolactone (1) in the presence of TMSOMe and TMSOTf to afford ort ho esters (23a-c), After-the conversion of the phthalimido functionality to the dibenzyl amino group, glucosylidene-glucosamine (25) was reduced with LiAlH4/AlCl3 to afford beta-(l --> 4)-glycoside (26) selectively.