Recent Advances on the Enantioselective Synthesis of C-Nucleosides Inhibitors of Inosine Monophosphate Dehydrogenase (IMPDH)

Abstract

This review will describe the recent advances in the synthesis of C-nucleosides with inhibitory activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the biosynthesis of guanine nucleotides. The review will cover synthetic approaches of structural analogues showing modifications in the furanose ring as well as in the heterocyclic base. Heterocyclic sugar nucleoside analogues in which the furanose ring has been replaced by a different heterocyclic ring including aza analogues, thioanalogues as well as dioxolanyl and isoxazolidinyl analogues are also considered.

4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase

“…For the synthesis of 2- C -glycopyranosyl thiazoles, the addition of 2-metalated-thiazoles to glyconolactones, cyclocondensation of anhydro-aldononitriles with cysteine derivatives followed by oxidation, and the reaction of anhydro-aldonothioamides with α-haloketones are the most frequently used procedures. According to the latter method, C -glucopyranosyl thioformamide 17 (Scheme ) was reacted with phenacyl bromide or 2-bromo-acetonaphthone to give high yields of the protected 2-β- d -glucopyranosyl thiazoles 18a and 18b , whose deprotection by the Zemplén method furnished the test compounds 10a and 10b , respectively.…”