Synthesis and Evaluation as Glycosidase Inhibitors of 1 H ‐Imidazol‐2‐yl C ‐Glycopyranosides

The (1 H ‐imidazol‐2‐yl)ulose 8 and the 1 H ‐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 m M , respectively), while 23 is a competitive inhibitor of yeast α‐glucosidase (pH 6.8, K i ≈ 0.26 m M ). Addition of 2‐lithiated 1‐[(dimethylamino)methyl]‐1 H ‐imidazole to 6 gave the ulose 7 (68%), which was deprotected to 8 . Reduction of 7 with NaBH 4 yielded a 12:88 mixture 10/11 . Attempts to selectively mesylate HOC(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 .