Enantiospecific synthesis of 1-deoxythiomannojirimycin from a derivative of D-glucose

Article abstract of DOI:10.1016/0008-6215(93)80025-A

1-Deoxythiomannojirimycin [2, (2R,3S,4R,5S)-3,4,5-trihydroxy-2-hydroxymethylthiane], a thio analogue of the glycosidase inhibitor 1-deoxymannojirimycin [1, (2R,3S,4R,5S)-3,4,5-trihydroxy-2-hydroxymethylpiperidine], has been synthesised from methyl 2-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside. The key reactions involved inversion of configuration at C-2 with the introduction of a thio function and cyclisation to give methyl 2,6-anhydro-2-thio-α-D-mannopyranoside (12). Hydrolysis of the 3,4-di-O-benzyl derivative (15) of 12 and reduction of the product with borohydride gave (2R,3S,4R,5S)-3,4-dibenzyloxy-5-hydroxy-2-hydroxymethylthiane (18). Hydrogenolysis of 18 yielded 2, which was a weak competitive inhibitor of yeast α-D-glucosidase but was inactive against almond β-D-glucosidase. 1-Deoxythiomannojirimycin [2, (2R,3S,4R,5S)-3,4,5-trihydroxy-2-hydroxymethylthiane], a thio analogue of the glycosidase inhibitor 1-deoxymannojirimycin [1, (2R,3S,4R,5S)-3,4,5-trihydroxy-2-hydroxymethylpiperidine], has been synthesised from methyl 2-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside. The key reactions involved inversion of configuration at C-2 with the introduction of a thio function and cyclisation to give methyl 2,6-anhydro-2-thio-α-D-mannopyranoside (12). Hydrolysis of the 3,4-di-O-benzyl derivative (15) of 12 and reduction of the product with borohydride gave (2R,3S,4R,5S),-3,4-dibenzyloxy-5-hydroxy-2-hydroxymethylthiane (18). Hydrogenolysis of 18 yielded 2. which was a weak competitive inhibitor of yeast α-D-glucosidase but was inactive against almond β-D-glucosidase.