Method for catalytic asymmetric synthesis of phosphorus-stereogenic (P-stereogenic) nucleoside derivative and catalyst used therein

1. A method for preparing a phosphorus-stereogenic (P-stereogenic) nucleoside derivative of formula (3), comprising:

subjecting a nucleoside and phosphoryl chloride to asymmetric reaction in a solvent under the catalysis of a chiral bicyclic imidazole catalyst in the presence of a base to obtain the P-stereogenic nucleoside derivative of formula (3):

wherein the base is an inorganic base, and the inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, disodium hydrogen phosphate, sodium bicarbonate and potassium bicarbonate.

2. The method of claim 1 , wherein the chiral bicyclic imidazole catalyst is selected from the group consisting of:

3. The method of claim 2 , wherein C1-C18 are all in S configuration.

4. The method of claim 1 , wherein the solvent is selected from the group consisting of methylbenzene, diethyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, dichloromethane, trichloromethane, 1,2-dichloroethane, ethyl acetate, acetone, acetonitrile and a combination thereof.

5. The method of claim 1 , wherein a molar ratio of the chiral bicyclic imidazole catalyst to the nucleoside is 1:(5˜100).

6. The method of claim 1 , wherein a molar ratio of the nucleoside to the phosphoryl chloride is 1:(0.5˜3.0); and a molar ratio of the nucleoside to the base is 1:(1.0˜4.0).

7. The method of claim 1 , wherein the asymmetric reaction is performed at −100˜80° C. for 1-72 h.