Efficient Syntheses of (E)-5-(2-Bromovinyl)-2′-deoxy-4-thiouridine; A Nucleoside Analogue with Potent Biological Activity

Abstract

(E)-5-(2-Bromovinyl)-2′-deoxy-4′-thiouridine (S-BVDU) is a potent antiherpesvirus agent and its use in gene therapy as an anticancer agent has recently been described. We here outline 2 efficient methods for the synthesis of S-BVDU. The decision as to which method is to be used depends upon the starting materials available but starting from BVU, an overall yield of β-nucleoside of 35% can be expected. From 5-ethyl-2′deoxy-4-thiouridine, radical bromination using bromine will give a quantitative conversion to S-BVDU if unreacted starting material is recycled (50%) or using N-bromosuccinimide, a one step yield in excess of 80% can be obtained.