Efficient syntheses of (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine; a nucleoside analogue with potent biological activity.
(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 beta-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.
Basnak
I
I
School of Chemistry, University of Birmingham, Edgbaston, UK.
Otter
G P
GP
Duncombe
R J
RJ
Westwood
N B
NB
Pietrarelli
M
M
Hardy
G W
GW
Mills
G
G
Rahim
S G
SG
Walker
R T
RT
D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006561:Herpes Simplex / Q000821:virology*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*; D010430:Pentosyltransferases / Q000378:metabolism; D013891:Thiouridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; C088044:5-(2-bromovinyl)-2'-deoxy-4'-thiouridine; D013891:Thiouridine; C020235:brivudine; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase; D001973:Bromodeoxyuridine