Application of solid-phase chemistry for the synthesis of 3'-fluoro-3'-deoxythymidine.
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.
Agarwal
Hitesh Kumar
HK
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island 02881, USA.
Parang
Keykavous
K
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
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D011108:Polymers; D015215:Zidovudine; D014269:Trifluoroacetic Acid; C002854:alovudine; D013936:Thymidine