ORGN 640 |
| 5¢-5¢-Dinucleoside phosphodiesters are naturally signaling and regulatory molecules. These compounds have been used in nucleic acid research and in designing prodrugs of nucleoside analogues. To avoid lengthy protection and deprotection reactions in the synthesis of these compounds, to minimize purification steps, and to increase the diversity of the synthesized compounds, a solid-phase method was designed to synthesize symmetrical 5¢-5¢-dinucleoside monophosphodiesters. Furthermore, this approach allowed the synthesis symmetrical 5¢-5¢-dinucleoside diphosphodiesters, triphosphodiesters, and tetraphosphodiesters. Four classes of phosphitylating reagents were subjected to reactions with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound mono-, di-, tri-, and tetraphosphitylating reagents. The solid-phase reagents were reacted with unprotected nucleosides (e.g., thymidine, adenosine, 3¢-azido-3¢-deoxythymidine, cytidine or inosine) in the presence of 5-(ethylthio)-1H-tetrazole. Polymer-bound nucleosides underwent oxidation with tert-butyl hydroperoxide, followed by deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford symmetrical 5¢-5¢-dinucleoside mono-, di-, tri-, and tetraphosphodiesters in 59-78% isolated yields.
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Asymmetric Reactions, Combinatorial Chemistry, Molecular Recognition and Self-Assembly, Proteins, Peptides, Amino Acids and Enzyme Inhibitors
8:00 PM-10:00 PM, Wednesday, March 28, 2007 Hyatt Regency Chicago -- Riverside Center, Poster
Division of Organic Chemistry |
