title: Application of solid-phase chemistry for the synthesis of 3'-fluoro-3'-deoxythymidine.
abstract: Reported solution-phase methods for the synthesis of 3'-fluoro-3'-deoxythymidine (FLT) are cumbersome, require purification of intermediates, and include several protecting/deprotecting steps. To circumvent these problems, a solid-phase strategy was designed for the synthesis of FLT. Thymidine was immobilized on trityl resin via the 5'-hydroxyl group. The subsequent mesylation of the free 3'-hydroxyl group in the presence of methanesulfonyl chloride afforded the polymer-bound 3'-O-mesylthymidine. Nucleophilic substitution of the mesyl moiety by hydroxyl group in the presence of sodium hydroxide produced the polymer-bound threothymidine. Fluorination with diethylaminosulfur trifluoride followed by acidic cleavage of the polymer-bound FLT in the presence of trifluoroacetic acid afforded FLT.
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island 02881, USA.
authors: Hitesh Kumar
authors: HK
authors: Agarwal
authors: Keykavous
authors: K
authors: Parang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D008956:Models, Chemical; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry; D013936:Thymidine / Q000737:chemistry; D014269:Trifluoroacetic Acid / Q000737:chemistry; D015215:Zidovudine / Q000031:analogs & derivatives
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D011108:Polymers; D015215:Zidovudine; D014269:Trifluoroacetic Acid; C002854:alovudine; D013936:Thymidine