合成路线1

5) The thermal rearrangement of 3-bromo-4,6-dimethyl-2-oxo-2H-pyran-5-carboxylic acid ethyl ester (XXXIX) with NaOH in refluxing water gives (rac)-trans-3-methylenecyclopropane-1,2-dicarboxylic acid (XL), which was submitted to optical resolution with (R)-alpha-methylbenzylamine (XLI) yielding, after crystallization, the corresponding (R,R)-enantiomeric salt (XLII). The decomposition of the salt and esterification of the free acid with trimethyl orthoformate affords (1R-trans)-3-methylenecyclopropane-1,2-dicarboxylic acid dimethyl ester (XLIII), which is reduced with LiAlH4 in THF to (1R-trans)-3-methylenecyclopropane-1,2-dimethanol (XLIV). The esterification of (XLIV) with benzoic anhydride and triethylamine in ethyl acetate affords the corresponding dibenzoate (XLV), which is epoxidized with m-chloroperbenzoic acid (MCPBA) in dichloromethane to afford the oxirane (XLVI). The isomerization of (XLVI) by means of LiI in ethyl acetate gives (2S-trans)-2,3-bis(benzoyloxymethyl)cyclobutanone (IX), which is reduced with lithium trisiamylborohydride in THF yielding [1S-(1alpha,2beta,3beta)]-3-hydroxycyclobutane-1,2-dimethanol 1,2-dibenzoate ester (X). The reaction of (X) with p-toluenesulfonyl chloride in pyridine affords the corresponding tosylate (XI), which is condensed with 6-O-benzylguanine (XII) by means of K2CO3 and 18-crown-6 in DMF yielding the substituted guanine (XIII). Finally, this compound is deprotected by treatment first with sodium methoxide in hot methanol, and then with 3N HCl.