Synthesis and evaluation as glycosidase inhibitors of 1H-imidazol-2-yl C-glycopyranosides

Article abstract of DOI:10.1002/hlca.19950780707

The (1H-imidazol-2-yl)ulose 8 and the 1H-imidazol-2-yl C-glycopyranosides 23 and 24 have been prepared from tetra-O-benzylgluconolactone 6 in two and six steps, respectively. The imidazoles 8 and 24 are moderate competitive inhibitors of sweet-almond β-glucosidase (pH 6.8, K(i) ~ 0.79 and 0.64 mM, respectively), while 23 is a competitive inhibitor of yeast α-glucosidase (pH 6.8, K(i) ~ 0.26 mM). Addition of 2-lithiated 1-[(dimethylamino)methyl]-1H-imidazole to 6 gave the ulose 7 (68%), which was deprotected to 8. Reduction of 7 with NaBH₄ yielded a 12:88 mixture 10/11. Attempts to selectively mesylate HO-C(1) of these diols failed, while dinitrobenzoylation led to 19/20, which cyclized easily (NaH) to a 25 :75 mixture of 21 and 22 which were separated and debenzylated to the C-glycosides 23 and 24.