Chemo-Enzymatic Synthesis and Biological Evaluation of 5,6-Disubstituted Benzimidazole Ribo- and 2′-Deoxyribonucleosides / I. D. Konstantinova, O. M. Selezneva, S. K. Kotovskaya, Z. M. Baskakova, V. N. Charushin, A. V. Baranovsky // Synthesis. - 2012. - Vol.45. - Article in press Кл.слова (ненормированные): 5,6-DISUBSTITUTED BENZIMIDAZOLES -- NUCLEOSIDES -- PURINE NUCLEOSIDE PHOSPHORYLASE Аннотация: A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic- bases showed good substrate activity for PNP and the ribo- and 2′-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-D-ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-D-ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2-deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cy \\\\expert2\\nbo\\Synthesis\\2012, Article in press.pdf |