title: Expedient and generic synthesis of imidazole nucleosides by enzymatic transglycosylation.
abstract: A straightforward route to original imidazole-based nucleosides that makes use of an enzymatic N-transglycosylation step is reported in both the ribo- and deoxyribo-series. To illustrate the scope of this approach, a diverse set of 4-aryl and 4-heteroaryl-1H-imidazoles featuring variable sizes and hydrogen-bonding patterns was prepared using a microwave-assisted Suzuki-Miyaura cross-coupling reaction. These imidazole derivatives were examined as possible substrates for the nucleoside 2'-deoxyribosyltransferase from L. leichmannii and the purine nucleoside phosphorylase from E. coli. The optimum transglycosylation conditions, including the use of co-adjuvants to address solubility issues, were defined. Enzymatic conversion of 4-(hetero)arylimidazoles to 2'-deoxyribo- or ribo-nucleosides proceeded in good to high conversion yields, except bulky hydrophobic imidazole derivatives. Nucleoside deoxyribosyltransferase of class II was found to convert the widest range of functionalized imidazoles into 2'-deoxyribonucleosides and was even capable of bis-glycosylating certain heterocyclic substrates. Our findings should enable chemoenzymatic access to a large diversity of flexible nucleoside analogues as molecular probes, drug candidates and original building blocks for synthetic biology.
authors.affiliation: Unité de Chimie et Biocatalyse, Institut Pasteur, CNRS, UMR3523, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. sylvie.pochet@pasteur.fr.
authors.forename: S
authors.initials: S
authors.lastname: Vichier-Guerre
authors.forename: L
authors.initials: L
authors.lastname: Dugué
authors.forename: F
authors.initials: F
authors.lastname: Bonhomme
authors.forename: S
authors.initials: S
authors.lastname: Pochet
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006031:Glycosylation; D007093:Imidazoles / Q000138:chemical synthesis*; D009705:Nucleosides / Q000138:chemical synthesis*; D010430:Pentosyltransferases / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D009705:Nucleosides; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase