title: Synthesis and antiviral evaluation of α-L-2'-deoxythreofuranosyl nucleosides.
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.
authors.affiliation: Laboratory for Medicinal Chemistry, FFW, UGent, Harelbekestraat 72, 9000 Gent, Belgium.
authors.forename: Kiran S
authors.initials: KS
authors.lastname: Toti
authors.forename: Marco
authors.initials: M
authors.lastname: Derudas
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043402:Cathepsin A / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D043402:Cathepsin A