IMPROVED SYNTHESES OF 5-THIO-D-GLUCOSE

Two convenient and improved routes for the synthesis of 5-thio-D-glucose are described starting with 5,6-anhydro-3-O-benzyl-1,2-O-isopropylidene-β-L-idofuranose (II). II reacts with thiourea in methanol to give 3-O-benzyl-5,6-dideoxy-5,6-epithio-1,2-O-isopropylidene-α-D-glucofuranose (III) which, on nucleophilic ring opening with potassium acetate in acetic acid-acetic anhydride, gives 6-O-acetyl-5-S-acetyl-3-O-benzyl-1,2-O-isopropylidene-5-thio-α-D-glucofuranose (IV), Reduction of IV with sodium in liquid ammonia, followed by hydrolysis in 0.5 M sulfuric acid, gives 5-thio-D-glucopyranose (VI) in 32% over-ail yield from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose. On reaction with sodium in benzyl alcohol, followed by p-tolylsulfonylation, II gives 3,6-di-O-benzyl-1,2-O-isopropylidene-5-O-(p-tolylsulfonyl)-O-L-idofuranose (X). Nucleophilic displacement of the p-tolylsulfonyloxy group with thiolacetate anion in dry N,N-dimethylformamide (DMF) gives 5-S-acetyl-3,6-di-O-benzyl-1,2-O-isopropylidene-5-thio-α-D-glucofuranose (XI). Reduction of XI with sodium in liquid ammonia, followed by hydrolysis in 0.05 M sulfuric acid, gives VI. © 1969, American Chemical Society. All rights reserved.