合成路线1

Reaction of L-xylose (XXII) with acetone and H2SO4 gives the acetonide (XXIII), which by acylation with benzoyl chloride in pyridine/chloroform yields the dibenzoate (XXIV). The hydrolysis of acetonide (XXIV) with acetic acid to the dihydroxy sugar (XXV) followed by acylation with acetic anhydride provides the tetracylated L-xylose (XXVI). Condensation of compound (XXVI) with 2,4-bis(trimethylsilyloxy)pyrimidine (XXVII) - obtained by silylation of uracil (XXVIII) with hexamethyldisilazane - by means of trimethylsilyl triflate in 1,2-dichloroethane affords nucleoside (XXIX). Selective hydrolysis of the acetate ester of compound (XXIX) using hydrazine and AcOH in pyridine yields the dibenzoylated xylofuranosyl-uracil (XXX). Isomerization of compound (XXX) to the arabinofuranosyl analogue (XXXI) is achieved by reaction with dicyclohexylcarbodiimide and dichloroacetic acid in DMSO/benzene, followed by treatment with NaBH4 in EtOH/benzene. Subsequent deoxygenation of the 2'-hy-droxyl group of compound (XXXI) to afford 2'-deoxynucleoside (XX) is effected via condensation with phenyl chlorothionoformate, and then reduction of the resulting thiocarbonate (XXXII) with tris(trimethylsilyl)silane and AIBN. Iodination of the uracil ring of (XX) with I2 and cerium ammonium nitrate (CAN) in acetonitrile produces the 5-iodo derivative (XXXIII), which is protected at the 3-nitrogen atom by condensation with p-toluoyl chloride to yield the protected nucleoside (XXXIV). Introduction of the 5-methyl group to give the thymidine derivative (XXXV) is then effected by reaction of the 5-iodouracil (XXXIV) with tetramethyltin in the presence of palladium catalyst. Finally, all protecting groups of compound (XXXV) are removed by treatment with methanolic ammonia.