ORGN 588 |
| Nucleosides and carbohydrates phosphodiesters are of considerable interest in nucleic acid research and the development of nucleosides with improved antiviral activity and prodrugs containing masked phosphates. Dinucleoside phosphodiesters appear to be more stable than nucleoside monophosphates to non-specific phosphohydrolases. Two classes of polymer-bound N,N-diisopropylamino-1,3,2-oxathiaphospholane were synthesized and were reacted with unprotected carbohydrates (e.g., mannose, melibiose) and nucleosides (e.g., adenosine, uridine, thymidine, AZT) in the presence of 1H-tetrazole. Oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent, followed by the 1,3,2-oxathiaphospholane ring-opening with the same or different nucleosides or carbohydrates in the presence of DBU, afforded the corresponding symmetrical or unsymmetrical dinucleoside and nucleoside-carbohydrate phosphodiesters and thiophosphodiesters derivatives through the elimination of polymer-bound ethylene episulfide in 36-70% overall yield. In total, by using different combinations of nucleosides and carbohydrates, 24 compounds (20 novel compounds) were synthesized. This strategy can be used to create the phosphodiester library of nucleosides and carbohydrates.
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Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster
Division of Organic Chemistry |
