A short synthesis of 1,3,4,6-tetra- O-acetyl-2-azido-2-deoxy-β- d-glucopyranose and the corresponding α-glucosyl chloride from d-mannose

Abstract

2-Acetamido-2-deoxy-D-glucopyranose is a constituent of many biologically important glycoconjugates. Chemical syntheses of model compounds related to these substances require glycosyl donors which favor the formation of either 1,2-cis or 1,2-tram glycosidic linkages. Glycosyl donors derived from 2-amino-2-deoxy-D-ghrcose that show a P-directing effect in the glycosylation reaction are relatively easily accessible’; more difficult to obtain are their a-directing counterparts. The 2-azido glycosyl halide approach is the most useful means for the stereoselective synthesis ofthe a-glycosidic linkage in the aminosugar series. According to this strategy’, the nonparticipating azido group is positioned at C-2 of the requisite monosaccharide, which is then converted into a glycosyl halide. After glycosylation, the azido group can be readily converted into a 2-amino or 2-acylamino function. According to the existing method?‘, however, the preparation of the precursors of glycosyl halide derivatives of 2-azido-2-deoxy-D-glucose is a tedious, multistep process. This, to a considerable extent, is because logical precursors such as the C-2 sulfonate derivatives of methyl cr-D-mannopyranoside do not undergo S,2 displacement reactions easily6,‘, and therefore cannot be used as intermediates to efficiently synthesize the corresponding 2-azido-2-deoxy-D-glucose derivatives. If an efficient inversion of the D-WZaW’Z0 to D-g/uco configuration is to be achieved by the S,2 displacement of a suitable leaving group, then the reaction should be carried out with a (usually less accessible) derivative ofg-D-mannose7. Recent critical evaluation” of the available routes to the precursors of glycosyl halides of 2-azido-2-deoxyhexoses found the azidonitration method’ most advantageous. That procedure, however, requires resolution of a complex mixture of products by chromatography. This laboratory has recently reported’ that treatment of 1,3,4,6-tetra-O-acetyI_PD-mannopyranose (1) with diethylaminosulfur trifluoride (DAST) afforded the corre-