A SHORT HIGH-YIELDING SYNTHESIS OF THE POTENT ANTI-VZV CARBOCYCLIC NUCLEOSIDE ANALOG CARBA-BVDU

A short high yielding synthesis of the potent anti-varicella-zoster vi rus (VZV) carbocyclic nucleoside analogue carba-BVDU 1 starting from a minodiol 2 is described. Reaction of 2 with acyl carbamate 3 and subse quent ring closure under acidic conditions afforded 5-ethyl-2'-deoxy-4 'a-carbauridine 5. In situ acetylation of 5 afforded ',5'-di-O-acetyl- 5-ethyl-2'-deoxy-4'a-carbauridine 6 in 78% overall yield from 2. Radic al bromination of 6 with either bromine or NBS and subsequent treatmen t with triethylamine gave an efficient conversion to tyl-5-(E)-(2-brom ovinyl)-2'-deoxy-4'a-carbauridine 7. Deacetylation of 7 afforded 1 in an overall 45-53% yield from 2.