CARB 5 |
| 3¢-Fluoro-2¢,3¢-dideoxythymidine (FLT) has been reported to be one of the most active reverse transcriptase inhibitors of HIV in vitro. Reported approaches to FLT synthesis from thymidine include a variety of protecting groups. These strategies are time-consuming since all the intermediate compounds must be purified. To circumvent these problems, a solid-phase strategy was designed for the synthesis of FLT. 5¢-hydroxyl group of thymidine (1) was immobilized on trityl chloride resin (2) in the presence of pyridine to yield polymer-bound thymidine (3, 85%). Resin 3 was subjected to reaction with methanesulfonyl chloride in the presence of pyridine to afford polymer-bound 3'-mesylthymidine (4, 96%). The reaction of 4 with sodium hydroxide in DMF for 48 h gave polymer-bound threothymidine (5, 96%). DAST was added to suspended resin 5 in dry benzene and anhydrous THF to produce polymer-bound FLT (6). Acidic cleave of trityl resin with TFA/DCM (3%) afforded FLT (7, 45%).
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Nucleosides, Nucleotides and Oligonucleotides
9:00 AM-11:40 AM, Sunday, 10 September 2006 Hilton San Francisco -- Yosemite C, Oral
Division of Carbohydrate Chemistry |
