合成路线1

An asymmetric synthesis of the (Z)(R)-enantioner has also been reported. Treatment of bromide (XXI) with NaOEt in Et2O provided ethyl methylenecyclopropanecarboxylate (XXII). Saponification of the ester group of (XXII) afforded racemic acid (XXIII) which, after activation as the mixed anhydride with isobutyl chloroformate, was coupled with (R)-phenylglycinol (XXIV) to yield a mixture of diastereomeric amides (XXV) and (XXVI). Chromatographic separation of the desired (R,R)-diastereoisomer (XXV) was followed by acid hydrolysis to furnish the (R)-acid (XXVII), which was subsequently esterified to (XXVIII) in ethanolic HCl. Addition of Br2 to (XXVIII) produced a mixture of (1S,2S)- and (1S,2R)-dibromoesters (XXIX). Further reduction of (XXIX) to alcohols (XXX) with DIBALH was followed by acetylation with Ac2O in pyridine yielding (XXXI). The alkylation-elimination procedure of the resulting bromides (XXXI) with adenine (V) afforded a mixture of (Z)(R) (XXXII) and (E)(R)- (XXXIII) olefins. Finally, deacetylation with ammonia in MeOH gave a mixture of the target (Z)(R)-compound and the corresponding E-isomer (XXXIV), which were not separed but used for analytical confirmation of the configuration of the title compound.