Synthesis of 2-(β-d-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles for inhibition of glycogen phosphorylase

• Preparation of aromatic aldehyde 4-(β-d-glucopyranosyl)semicarbazones.
• Synthesis of 2-(β-d-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles.
• Low micromolar inhibitors of glycogen phosphorylase.

Aromatic aldehyde 4-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)semicarbazones were synthesized by the addition of different hydrazones onto O-peracetylated β-d-glucopyranosyl isocyanate. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles. Removal of the O-acetyl protecting groups under Zemplén conditions gave test compounds to show low micromolar inhibition against rabbit muscle glycogen phosphorylase b. Best inhibitors of these series were 4-(β-d-glucopyranosyl)semicarbazones of 4-nitrobenzaldehyde (Ki = 4.5 μM), 2-naphthaldehyde (Ki = 5.5 μM) and 2-(β-d-glucopyranosylamino)-5-(4-methylphenyl)-1,3,4-oxadiazole (Ki = 12 μM).

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