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

Abstract

1-Deoxythiomannojirimycin [ 2, (2 R,3 S,4 R,5 S)-3,4,5-trihydroxy-2-hydroxymethylthiane], a thio analogue of the glycosidase inhibitor 1-deoxymannojirimycin [ 1, (2 R,3 S,4 R,5 S)-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) or 12 and reduction of the product with borohydride gave (2, R,3 S,4 R,5 S)-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.