合成路线1

In a different protection strategy, (diethoxyethyl)malonate (XIX) was obtained by alkylation of diethyl malonate (XVII) with bromoacetaldehyde diethyl acetal (XVIII). Reduction of the ester groups of (XIX) with LiBH4 provided diol (XX). The asymmetric mono-acetate ester (XXI) was generated by enantioselective acylation of the prochiral diol (XX) with vinyl acetate in the presence of lipase PS 30. Reaction of the free hydroxyl of (XXI) with p-toluenesulfonyl chloride afforded tosylate (XXII), which was subsequently condensed with 2-amino-6-chloropurine (I), yielding adduct (XXIII). Conversion of the chloropurine ring of (XXIII) to the target guanine derivative (XXV) was achieved by displacement of the chloro group with benzyl alcohol, with concomitant acetate ester hydrolysis, followed by hydrogenolytic cleavage of the resultant benzyl ether (XXIV). Alternatively, initial acetate ester hydrolysis in (XXIII) gave alcohol (XXVI), which was further subjected to chloro group hydrolysis in the presence of either KOH or tertiary amines to yield (XXV). Conversion of alcohol (XXV) to the target stearate ester (XXVIII) was achieved by treatment with stearoyl chloride (IX) or with the mixed anhydride of stearic acid (XXVII) with pivaloyl chloride or with tosyl chloride.