合成路线1

(S)-Glycidol (I) was selectively opened by Li2NiBr4 at 0 C to provide (S)-3-bromo-1,2-propanediol (II). Subsequent reaction of (II) with trimethyl orthoformate in the presence of p-toluenesulfonic acid generated the dioxolane (III) as a 1:1 mixture of cis and trans orthoesters. The methoxy orthoester (III) was further converted to the isopropoxy analogue (IV) by treatement with isopropanol under acidic conditions. Introduction of the phosphonate group in (IV) was achieved by means of a ZnCl2-catalyzed Arbuzov reaction with triisopropyl phosphite and phosphorus trichloride to give a 2:5 mixture of cis (V) and trans (VI) phosphonates, which were separated by flash chromatography. Displacement of cis bromide (V) with 2-amino-6-chloropurine (VII) in the presence of Cs2CO3 in DMF at 60 C provided compound (VIII). The phosphonate ester of (VIII) was then deprotected by treatment with ISiMe3, followed by aqueous hydrolysis of the intermediate silyl phosphonate (IX) and concomitant hydrolysis of the 6-chloropurine to guanine (X). Finally, absorption on a Sephadex DEAE A-25 column, followed by elution with ammonium bicarbonate solution, provided the title ammonium salt.