A Short High Yielding Synthesis of the Potent Anti-VZV Carbocyclic Nucleoside Analogue Carba-BVDU |
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| Authors: | P G Wyatt A S Anslow B A Coomber R PC Cousins D N Evans V S Gilbert |
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| Institution: | 1. Department of Medicinal Chemistry II , Glaxo Wellcome plc, Glaxo Wellcome Medicines Research Centre , Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK;2. Process Research Department , Glaxo Wellcome plc, Glaxo Wellcome Medicines Research Centre , Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK |
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| Abstract: | Abstract A short high yielding synthesis of the potent anti-varicella-zoster virus (VZV) carbocyclic nucleoside analogue carba-BVDU 1 starting from aminodiol 2 is described. Reaction of 2 with acyl carbamate 3 and subsequent ring closure under acidic conditions afforded 5-ethyl-2′-deoxy-4′a-carbauridine 5. In situ acetylation of 5 afforded 3′,5′-di-O-acetyl-5-ethyl-2′-deoxy-4′a-carbauridine 6 in 78% overall yield from 2. Radical bromination of 6 with either bromine or NBS and subsequent treatment with triethylamine gave an efficient conversion to 3′,5′-di-O-acetyl-5-(E)-(2-bromovinyl)-2′-deoxy-4′a-carbauridine 7. Deacetylation of 7 afforded 1 in an overall 45–53% yield from 2. |
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