Novel conversion of aldopyranosides into 5-thioaldopyranosides via acyclic monothioacetals with inversion and retention of configuration at C-5

Article abstract of DOI:10.1016/0008-6215(95)00386-X

A new strategy for synthesis of 5-thioaldopyranosides was developed. This included the ring opening of D-aldopyranosides with dimethylboron bromide and thioacetic acid, giving the acyclic monothioacetals, followed by the intramolecular cyclization between C-5 and 1-S. Cyclization with inversion of configuration at C-5 was achieved by simultaneous S-deacetylation and intramolecular nucleophilic substitution of the 5-methanesulfonylated monothioacetal to give 5-thio-L-aldopyranosides. The 5-hydroxymonothioacetal underwent cyclization with the Mitsunobu reagents to give the same 5-thio-L-aldopyranosides. Syntheses of 5-thio-D-glucopyranosides were achieved by double inversion of C-5. The glycos-5-ulose derivatives of the monothioacetals spontaneously cyclized on S-deacetylation to give 5-C-hydroxyl-5-thio-D-glucopyranosides, which were deoxygenated at C-5 to give 5-thio-D-glucopyranosides, with net retention of configuration at C-5 from the monothioacetal. Stereoselective reduction of the glycos-5-ulose followed by intramolecular cyclization with the Mitsunobu reagents also gave 5-thio-D-glucopyranosides. The strategy for L enantiomers was applied to the synthesis of 5-thio-L-galactose. The inhibitory effect of 5-thio-L-galactose toward α-L-fucosidase (K(i) 960 μM) is also reported.