合成路线1

Alkylation of adenine (I) by means of (R)-propylene carbonate (II) in the presence of NaOH in hot DMF provided (R)-9-(2-hydroxypropyl)adenine (III). This was condensed with tosylate (IV) using magnesium tert-butoxide to furnish the alkoxymethylphosphonate (V). Phosphonic acid (VI) was then obtained by hydrolysis of the phosphate ester groups with bromotrimethylsilane. Monophenyl phosphonate (IX) was prepared by either coupling of acid (VI) with phenol (VII) in the presence of DCC or by previous activation of (VI) with SOCl2, and then coupling with phenoxytrimethylsilane (VIII). Further activation of (IX) with SOCl2 to give (X), followed by its condensation with L-alanine isopropyl ester (XI), yielded phosphonamide (XII) as a mixture of diastereomers. The title isomer was then isolated by several alternative procedures, including column chromatography over various supports and fractional crystallization.