合成路线1

A new practical asymmetric synthesis of lubocavir has been described: The diastereoselective cycloaddition of (-)-dimenthyl fumarate (I) with ketene dimethylacetal (II) by means of diisobutylaluminum chloride (DIBAC) in toluene gives the cyclobutane (III), which is reduced with LiAlH4 yielding the cyclobutyl dicarbinol (IV). The reaction of (IV) with benzoyl chloride affords the dibenzoate (V), which is deprotected in acidic medium to give the cyclobutanone (VI). The stereoselective reduction of (VI) with DIBAC yields the chiral cyclobutanol (VII), which is treated with triflic anhydride to afford the activated triflate (VIII). The regioselective condensation of (VIII) with 2-amino-6-iodopurine benzyltriethylammonium salt (IX) gives the expected addition product (X), which is debenzoylated with NaOMe in methanol yielding the 2-amino-6-methoxypurine (XI). Finally, this compound is converted to lobucavir by refluxing with aqueous hydrochloric acid.