合成路线1

Regiospecific opening of the chiral 2-(benzyloxymethyl)oxirane (I) with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate afforded phosphonate (III). After conversion of (III) to the chloromethyl ether (IV), upon treatment with paraformaldehyde and HCl, condensation with the sodium salt of 2-amino-6-chloropurine (V) gave the nucleoside phosphonate (VI). Simultaneous hydrogenolysis of the chlorine atom and benzyl ether of (VI) by transfer hydrogenation in the presence of ammonium formate and Pd/C yielded (VII). The phosphonate ester groups of (VII) were then cleaved by means of bromotrimethylsilane to give phosphonic acid (VIII). Finally, intramolecular cyclization of (VIII) by treatment with DCC furnished the title compound.