Issue 14, 2016

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.

Graphical abstract: Expedient and generic synthesis of imidazole nucleosides by enzymatic transglycosylation

Supplementary files

Article information

Article type
Paper
Submitted
21 Feb 2016
Accepted
11 Mar 2016
First published
11 Mar 2016

Org. Biomol. Chem., 2016,14, 3638-3653

Expedient and generic synthesis of imidazole nucleosides by enzymatic transglycosylation

S. Vichier-Guerre, L. Dugué, F. Bonhomme and S. Pochet, Org. Biomol. Chem., 2016, 14, 3638 DOI: 10.1039/C6OB00405A

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