Chemo-enzymatic Synthesis Of Uridine Monophosphate

Ribose is a kind of pentose which is widespread in the nature and involved in every biological life activities and it’s also a major component of the nucleosides. Uridine monophosphate is composed of ribose, phosphate and pyrimidine base, Derivatives synthesized form uridine monophosphate have great medical values in anti-viral and tumor antagonism. It’s necessary to build up an effectively synthesis process of UMP, because the natural nucleoside source is limited, and the price is expensive, In this study, we studied the best conditions of technological process to synthesis uridine monophosphate from D-ribose.Firstly, the process of synthesizing hybrid configuration of1-methoxy-D-ribose from D-ribose was studied. Methylations of hydrogen chloride, oil of vitriol and thionyl chloride in methanol were compared and the results shew that, the best methylation reagent is1mol/L hydrogen chloride/methanol solution, we studied the protecting conditions of1-OMe- D-ribose, synthesized1-O-acetyl-2,3,5-tri-O-benzyl-D-ribofuranose,1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose,1-O-acetyl-2,3,5-tri-O-(4-chlo-robenzoyl)-P-D-ribofuranose and1,2,3,5-tetra-O-acetyl-D-ribofuranose, the best conditions were conformed.Secondly, we synthesized1-Cl-2,3,5-O-tris-benzoyl-D-ribofuranose,1,3,5-O-tris-benzoyl-D-ribofuranose and1,3,5-O-tris-(4-chlorobenzoyl)-D-ribofuranose from1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose and1-O-acetyl-2,3,5-tri-O-(4-chlorobenzoyl)-β-D-ribofuranose by reacted with dry hydrogen chloride in dichloromethane at0℃, obtained oleaginous product1-Cl-2,3,5-O-tris-benzoyl-D-ribofuranose which was unstable in air so it was better to dissolve the product in aether for a while then to crystallize and changed to1,3,5-O-tris-benzoyl-D-ribofuranose, the yield was72%. We also obtained1-Cl-2,3,5-O-tris-(4-chlorobenzoyl)-D-ribofur-anose by reacted in dichloromethane with passing dry hydrogen chloride for2.5h at0℃, the yield was84.9%, and it is more fit to synthesis D-ribose-1-phosphate.Finally, the technological conditions of synthesizing of uridine mono-phosphate from1-O-acetyl-2,3,5-tri-O-(4-chlorobenzoyl)-β-D-ribofuranose were studied. Uracil reacted with HMDS under reflux, then the suger reacted with protected uracil under the catalysis of SnCl4in C2H4Cl2to obtain2’,3’,5’-tri-O-(4-chlorobenzoyl)-uridine, the yield was83%, removed chlorobenzoyl with NaOMe in MeOH solution to get uridine and the yield was54%. For synthesizing uridine monophosphate,2’,3’-O-isopropylidene-uridine was synthesized from uridine, the yield was81.3%, then reacted with orthophosphate at the existence of phosphorus pentoxide and4A molecular-bolt in acetonitrile, later barium hydroxide was used to neutralize the redundant orthophosphate. Removed isopropylidenes in1mol/L hydrochloric acid, dried by phosphorus pentoxide and few sodium hydroxide solid, then crystallized in ethanol and obtained uridine monophosphate, the yield was79%.