合成路线1

The selective tosylation of D-mannose (I) with Ts-Cl in pyridine gives 6-O-tosyl-D-mannose (II), which is cyclized by means of NaOH in pyridine/water, yielding 1,6-anhydro-D-mannose (III) (1). The protection of (III) with 2,2-dimethoxypropane (IV) and TsOH in acetone gives the isopropylidene ketal (V), which is acylated with benzoyl chloride in pyridine, yielding benzoate (VI). The deprotection of (VI) with H2SO4 in dioxane affords 4-O-benzoyl-1,6-anhydro-D-mannose (VII), which is treated first with NaIO4 and then reduced with NaBH4, providing the dioxolane (VIII). This compound without isolation is rearranged in basic medium to the dioxolane (IX), which is selectively silylated with Tbdps-Cl to give the silyl ether (X). The hydrolysis of (X) with NaOMe in methanol yields the diol (XI), which is oxidized with NaIO4 and RuO2 in acetonitrile, affording the carboxylic acid (XII). The modified Hunsdiecker reaction of (XII) with Pb(OAc)4 in ethyl acetate yields the acetoxydioxolane (XIII) (2-4), which is condensed with 6-chloro-2-fluoro-9-(trimethylsilyl)purine (XIV) by means of Tms-OTf in dichloromethane to afford the nucleoside (XV). The reaction of (XV) with NH3 in dimethoxyethane gives the 2-amino-6-chloronucleoside (XVI), which is treated with NH3 in methanol to yield the 2,6-diaminonucleoside (XVII). Finally, this compound is desilylated with TBAF in THF.