Improved preparation of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the most efficient glucose analogue inhibitors of glycogen phosphorylase

Eszter Szennyes; Éva Bokor; Gyula Batta; Tibor Docsa; Pál Gergely; László Somsák

doi:10.1039/C6RA21839C

Improved preparation of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the most efficient glucose analogue inhibitors of glycogen phosphorylase

Eszter Szennyes,^a Éva Bokor,^a Gyula Batta,^a Tibor Docsa,^b Pál Gergely^b and László Somsák*^a

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* Corresponding authors

^a Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary
E-mail: somsak.laszlo@science.unideb.hu
Fax: +36 52512744
Tel: +36 52512900 ext. 22348

^b Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary

Abstract

The synthesis of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the currently most efficient glucose derived inhibitors of glycogen phosphorylase enzymes was amended and extended by using O-perbenzylated β-D-glucopyranosyl cyanide as the starting material. This compound and its derivatives C-(β-D-glucopyranosyl)formimidate and formamidine were obtained in large scale reactions to give the products in ∼20 grams amounts. Ring closing reactions of the formimidate and formamidine by α-amino- and α-bromoketones, respectively, produced the O-perbenzylated imidazoles which were deprotected by catalytic hydrogenation or by EtSH/BF₃·OEt₂. Newly prepared 4(5)-(4-nitro- and -aminophenyl)-2-(β-D-glucopyranosyl)-imidazoles proved less efficient inhibitors (K_i values of 1141 and 411 nM, respectively) than their unsubstituted counterpart (K_i = 280 nM).

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Publication details

The article was received on 31 Aug 2016, accepted on 28 Sep 2016 and first published on 29 Sep 2016

Article type: Paper

DOI: 10.1039/C6RA21839C

Citation: RSC Adv., 2016,6, 94787-94794

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Improved preparation of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the most efficient glucose analogue inhibitors of glycogen phosphorylase

E. Szennyes, É. Bokor, G. Batta, T. Docsa, P. Gergely and L. Somsák, RSC Adv., 2016, 6, 94787
DOI: 10.1039/C6RA21839C
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Improved preparation of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the most efficient glucose analogue inhibitors of glycogen phosphorylase

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Improved preparation of 4(5)-aryl-2-(β-D-glucopyranosyl)-imidazoles, the most efficient glucose analogue inhibitors of glycogen phosphorylase

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