European Journal of Medicinal Chemistry 2011-09-01

Synthesis and antiviral evaluation of α-L-2'-deoxythreofuranosyl nucleosides.

Kiran S Toti, Marco Derudas, Christopher McGuigan, Jan Balzarini, Serge Van Calenbergh

Index: Eur. J. Med. Chem. 46(9) , 3704-13, (2011)

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Abstract

The synthesis of a series of α-L-2'-deoxythreofuranosyl nucleosides featuring the nucleobases A, T, C and U is described in seven steps from 1,2-O-isopropyledene-α-L-threose, involving a Vorbrüggen coupling and a Barton-McCombie deoxygenation protocol as the key steps. All analogues, including a phosphoramidate nucleoside phosphate prodrug of the T analogue, were evaluated against a broad panel of different viruses but found inactive, while also lacking notable cellular toxicity. The thymidine analogue showed inhibition to mitochondrial thymidine kinase-2 (TK-2), herpes simplex virus type 1 (HSV-1) TK, varicella-zoster virus (VZV) TK and Mycobacterium tuberculosis thymidylate kinase.Copyright © 2011 Elsevier Masson SAS. All rights reserved.