ORGN 519 |
| New methodology for regiospecific and highly stereoselective glycosylation with 2-deoxyfuranose derivatives using the sodium salt method has been developed. The solubility of purine sodium salts in less polar solvents was enhanced by substitution of lipophilic groups on the polar bases and utilization of mixed solvents. The streoselectivty varied with alkyl group chain lengths. With a propyl group, regiospecfic and highly stereoselective glycosylations were achieved with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride. The high stereoselectivities were rationalized on the basis of solute/solvent polarities and differential solvation in binary solvent mixtures. The improved methodology has been applied for the synthesis of cladribine. Glycosylation of 2-chloro-6-(2-alkylimidazol-1-yl)purines (e.g., propyl, butyl, pentyl) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride in binary solvent mixtures gave the respective 2'-deoxy-β-nucleosides in excellent yields with high to complete stereoselectivity. Benzylation at N3' of the imidazolyl groups followed by ammonolysis gave cladribine in good to excellent yields. |
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New Reactions and Methodology, Heterocycles and Aromatics, Bioorganic Chemistry
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |