The Synthesis Of2-C-methyl-β-D-ribofuranose And Its Derivative

Nucleoside analogues derived from2-C-methyl-β-D-ribofuranose have higher biological activity in anti-cancer and anti-viral, moreover it plays a very important role in the anti-HCV drugs.2’-C-methyl cytidine with good prospects is one of them, which is the intermediate of multiple targeted anti-HCV drugs. Therefore, studying on the synthesis of2’-C-methyl cytidine is of great significance.By consulting domestic and foreign relevant literatures, summarizing the pros and cons of intermediate synthetic routes and similar reactions, ultimately determine that2’-C-methyl cytidine was synthesized from D-fructose by six steps, which were lactonization, acylation, reduction, acylation, condensation and deprotection, the overall yield was9.20%. Combining with the reduction mechanism, the best raw material for synthesizing2-C-Methyl-D-ribonic-y-lactone were D-fructose and CaO. Through single factor experiments determinted that triethylamine was the best acid binding agent for acylation reaction with the yield of85.50%. The conclusion that the best reductant for2,3,5-Tri-O-benzoyl-2-C-methyl-β-D-ribofuranose was Red-Al was obtained by comparing using three different reductants as LiAlH4, NaBH4and Red-Al and the yield can up to96.61%. The conclusion that BSA was the optimum silane reagent for2’,3’,5’-tri-O-benzoyl-2’-C-methyl-D-cytidine was obtained by investigating four silylating agents as TMSCl, TBDPSCl, HMDS, BSA,and the yield can reach96.90%. Finally through single factor determinted CH3ONa/CH3OH was the best de-protection system for alcoholysis reaction with the yield of89.59%.Influences of temperature, reaction time and material ratio were investigated, and best conditions were screened out. The characterization methods of IR、1HNMR、13C-NMR and MS were applied to confirm the structures of intermediates and products.