Synthesis Of 2'-deoxyuridine By Combined Chemical-biologic Method

Nucleosides and their analogues provide good activities of antitumor,antiviral and antibiosis,which play irreplaceable functions in clinical applications.The scientific study on synthesis of nucleoside drugs is a hot topic nowadays.This paper proposes the views of chemical and biological ways to synthesize nucleosides and their analogues based on wide ranges of previous literature collections.We firstly synthesized 2-deoxy-a-D-ribosyl-1-phosphate salt by crystallization-induced asymmetric transformation(CIAT)from 1-chloro-3',5'-di(4-chlorobenzoyl)-2-deoxy-D-ribose,Secondly,we adopted nucleoside phosphorylase to convert 2-deoxy-a-D-ribosyl-1-phosphate salt and basic group to nucleoside and its analogues by biological synthesis.We successfully synthesized 2-deoxy-a-D-ribosyl-1-phosphate salt by crystallization-induced asymmetric transformation from 1-chloro-3',5'-di(4-chlorobenzoyl)-2-deoxy-D-ribose then use nucleoside phosphorylase converts 2-deoxy-a-D-ribosyl-1-phosphate salt and uracil to deoxyuridine by biological synthesis on this paper.The optimum conditions in different processes of this experiments as following:(1)The optimum conditionsto synthesized 3',5'-di(4-chlorobenzoyl)-2-deoxy-?-D-ribose-1-phosphate tertiary butyl amine-are:the raw ratio of ribose-1-chloride:phosphoric acid:tertiary butyl amine is 1:3:3,when the dosage of ribose-1-chloride is 8.48 g the amount of acetonitrile is 120ml,reacted for 23 h.(2)The optimum conditions for synthesizing 3 ',5 '-di(4-chlorobenzoyl)-2-deoxy-?-D-ribose-1-phosphate cyclohexylamine is:the raw ratio of ribose-1-chlorid:cyclohexylamine is 1:3,under 0? reacted for 1 h.The yield of the product is 94.53%,purity is 95.68%.(3)The optimum conditions for synthesizing 2-deoxy-?-D-ribose-1-phosphate cyclohexylamine salt is:under 45 ? in methanol with 3%cyclohexylamine reacted 36 h.The yield of the product is 82.69%(4)The optimum conditions for synthesizing 2'-deoxyuridine:the concentration of uracil is 15mmol/L,the concentration of thallus is 15mmol/L the molar ratio of ribose-1-phosphoric:urial is 1:3,pH is 7.0,reaction temperature is 60?,reaction time is 6 h.The convertion rate is 42.32%by HPLC.By adopting the advantages of chemical and biological ways,above experiments have solved the impossible practice of obtaining single isomers by chemical synthesis ways,also avoiding mass poisonous reagents use.It provides us great significances on scientific researches and industrial applications with its high stereo selectivity,mild conditions and short period of reactions.