Synthesis of variously coupled conjugates of D-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase |
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Authors: | Kun Sándor Nagy Gergo Z Tóth Marietta Czecze Laura Van Nhien Albert Nguyen Docsa Tibor Gergely Pál Charavgi Maria-Despoina Skourti Paraskevi V Chrysina Evangelia D Patonay Tamás Somsák László |
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Institution: | Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary. |
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Abstract: | 5-(O-Perbenzoylated-β-D-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-D-glucopyranosyl cyanide by Bu(3)SnN(3) or Me(3)SiN(3)-Bu(2)SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated-β-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 NaN(3). These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplén protocol, β-D-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3-triazole, β-D-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-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-(β-D-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: K(i)=854μM, 2-(β-D-glucopyranosyl)-5-1-(naphthalen-2-yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: K(i)=745μM). |
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