Synthesis of (+)-nojirimycin from 2,3,4,6-tetra-O-benzyl-D-glucopyranose

Abstract

Synthesis of the antibiotic (+)-nojirimycin has been accomplished starting from commercially available 2,3,4,6-tetra-O-benzyl-D-glucopyranose 2. This D-glucopyranose derivative was converted into the D-xylo-hexos-5-ulose dimethyl acetal 5 by thioacetalisation, C-5 oxidation and transacetalisation with methanol. Introduction of the 5-amino substituent with the correct D-gluco-stereochemistry was realised by conversion of ketone 5 into the corresponding oxime 6, followed by diastereoselective reduction with lithium aluminium hydride. After protection of the resulting primary amine as its tert-butyl carbamate, the desired D-gluco-amine 7 could be separated from the unwanted L-ido-isomer 8. Hydrogenolysis of 7 followed by treatment with aqueous sulfur dioxide yielded 1-deoxynojirimycin-1-sulfonic acid 9, which was further transformed into (+)-nojirimycin 1.