Synthesis of variously coupled conjugates of D-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase

5-(O-Perbenzoylated-beta-D-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-beta-D-glucopyranosyl cyanide by Bu3SnN3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated-beta-D-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and asides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplen protocol, beta-D-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3-triazole, beta-D-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and beta-D-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4-oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(beta-D-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: K-i = 854 mu M, 2-(beta-D-glucopyranosyl)-5-[1-(naphthalen-2-yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: K-i = 745 mu M). (C) 2011 Elsevier Ltd. All rights reserved.