Synthesis of some derivatives of C-(1-deoxy-1-N-substituted-d-glucopyranosyl)formic acid (d-gluco-hept-2-ulopyranosonic acid) as potential inhibitors of glycogen phosphorylase

Per-O-benzoylated derivatives (amide, methyl ester and glycinamide) of C-(1-azido-1-deoxy-α-d-glucopyranosyl)formic acid obtained by azide substitution in the corresponding C-(1-bromo-1-deoxy-β-d-glucopyranosyl)formic acid derivatives were debenzoylated by the Zemplén-protocol. Per-O-benzoylated C-(1-azido-1-deoxy-α-d-glucopyranosyl)formamide was dehydrated by oxalyl chloride–DMF to give the corresponding nitrile, while from its reduction mixture obtained by Raney-nickel or sodium hydrogentelluride C-(1-amino-1-deoxy-β-d-glucopyranosyl)formamide could be isolated. Acetylation of this amino-amide by Ac2O/Py and subsequent debenzoylation gave C-(1-acetamido-1-deoxy-β-d-glucopyranosyl)formamide. Applying the same conditions to the crude reduction mixture allowed the α-anomer to be isolated as a minor component. An alternative pathway to produce the above β-anomer appeared in the reaction of C-(1-bromo-1-deoxy-β-d-glucopyranosyl)formamide with CH3CN in the presence of Ag2CO3 to yield 1-acetamido-2,3,4,6,-tetra-O-benzoyl-1-deoxy-β-d-glucopyranosyl cyanide, which was hydrated, in the presence of TiCl4, to the formamide. Some of the new compounds were shown to be weak inhibitors of muscle glycogen phosphorylase b.