SYNTHESIS AND EVALUATION AS GLYCOSIDASE INHIBITORS OF 1H-IMIDAZOL-2-YL C-GLYCOPYRANOSIDES

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 beta-glucosidase (pH 6.8, K-i approximate to 0.79 and 0.64 mM respectively), while 23 is a competitive inhibitor of yeast alpha-glucosidase (pH 6.8, K-i approximate to 0.26 mM). Addition of 2-lithiated 1-[(dimelhyl-amino)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.