Synthesis and antiviral evaluation of α-l-2'-deoxythreofuranosyl nucleosides
Toti, Kiran S × Derudas, Marco McGuigan, Christopher Balzarini, Jan Van Calenbergh, Serge #
European Journal of Medicinal Chemistry vol:46 issue:9 pages:3704-13
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.