.2 '- O - Methyl - Ribose Nucleoside Synthesis Research

2′-O-Methylribonucleosides are modified by methylation of ribonucleosides. 2′-O-Methylribonucleosides are widely distributed in RNA and DNA, and now have been extensively utilized as a second-generation oligonucleotide constructs due to their favorable in-vitro and in-vivo properties. They provide a better stability and also strong binding capability to the complementary gene targets. They have many pharmacological functions such as immunoregulation, antibacterial, diminish inflammation and kill tumours.In this dissertation, the synthesis ways of 2′-O-Methylribonucleosides were studied and summarized, and practical and feasible ways were designed. The synthesis of 2′-O-methyl adenosine was directly accomplished by methylation of adenosine with diazomethane without protection, then the isomers were isolated through ion exchange chromatography on Dowex 1-X2(OH~-), getting pure 2′-O-methyl adenosine. The synthesis of 2′-O-methyl guanosine, starting from guanosine through five steps. Firstly, acetylation of guanosine, protecting three hydroxyl of guanosine. Secondly, 2-amino-6-chloro-9-β-D-ribofuranosyl-purine has been prepared via chlorination using phosphorus oxychloride or sulfur dioxide, and deacetylation of 2′,3′,5′-tri-O-acetyl guanosine. Moreover, high regioselective methylation of 2-amino-6-chloro-9-β-D-ribofuranosyl-purine with diazomethane, getting 2-amino-6-chloro-9-[2′-O-methyl-β-D-ribofuranosyl]-purine. Then followed by hydrolysis provided 2′-O-methyl guanosine and 3′-O-methyl guanosine. The isomers were isolated through ion exchange chromatography on Dowex 1-X2(OH~-), getting pure 2′-O-methyl guanosine.The structure of the synthetic products were characterized by Melting Point(MP), Infrared Spectoscopy(IR), Mass Spectra(MS) and ~1H Nuclear Magnetic Resonance(NMR). The results proved: the structures and performance indicated that the products conformed to the design requirement.