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• 作者：Minghong Zhong ; Ireneusz Nowak ; Morris J. Robins
• 刊名：Journal of Organic Chemistry
• 出版年：2006
• 出版时间：September 29, 2006
• 年：2006
• 卷：71
• 期：20
• 页码：7773 - 7779
• 全文大小：107K
• 年卷期：v.71,no.20(September 29, 2006)
• ISSN：1520-6904

文摘

Glycosylation of 6-(substituted-imidazol-1-yl)purine sodium salts with 2-deoxy-3,5-di-O-(p-toluoyl)--D-erythro-pentofuranosyl chloride proceeds with regiospecific formation of the N9 isomers. Base substrateswith lipophilic substituents on the C6-linked imidazole moiety are more soluble in organic solvents, andthe solubility is further increased with binary solvent mixtures. Selective solvation also diminishes theextent of anomerization of the chlorosugar. Stirred reaction mixtures of the modified-purine sodium saltsgenerated in a polar solvent and cooled solutions of the protected 2-deoxysugar chloride in a nonpolarsolvent give 2'-deoxynucleoside derivatives with N9 regiochemistry and enhanced / configurationratios. Application of the binary-solvent methodology with 2-chloro-6-(substituted-imidazol-1-yl)purinesalts in cold acetonitrile and the chlorosugar in cold dichloromethane gives essentially quantitative yieldsof the N9 isomers of -anomeric 2'-deoxynucleoside intermediates. Direct ammonolysis (NH₃/MeOH)of such intermediates or benzylation of the imidazole ring followed by milder ammonolysis of theimidazolium salt gives high yields of the clinical anticancer drug cladribine (2-chloro-2'-deoxyadenosine).