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The reduction of 2-octyn-1-ol (XII) with bis(2-methoxyethoxy)aluminum hydride in toluene/THF gives 2-octen-1-ol (XIII), which is treated with tert-butyl hydroperoxide, (+)-diethyl L-tartrate and titanium tetraisopropoxide in dichloromethane yielding epoxide (XIV). The latter is reduced with bis(2-ethoxyethoxy)aluminum hydride in toluene/THF, affording the chiral diol (XV). The selective monotosylation of (XV) with TsCl in pyridine provides the primary tosylate (XVI), which is treated with NaI in hot acetone to furnish 1-iodo-3-octanol (XVII). Protection of (XVII) with dihydropyran and pyridine hydrochloride gives the tetrahydropyranyl ether (XVIII), which is condensed with dimethyl methylphosphonate (XIX) by means of BuLi and TEA in THF to yield the phosphonate (XX). Condensation of compound (XX) with 5-methoxy-2,3,3a,4-tetrahydronaphtho[2,3-b]furan-2-one (XXI) by means of BuLi in THF affords the tricyclic adduct (XXII), which is hydrogenated with H2 over Pd/C in ethanol to provide compound (XXIII). Isomerization of (XXIII) with NaOH in refluxing ethanol gives diastereomer (XXIV). The reduction of the carbonyl group of (XXIV) with NaBH4 in methanol, followed by deprotection with HOAc in THF yields compound (XXV). The demethylation of compound (XXV) by means of BuLi and Ph2PH in THF affords the tricyclic phenol (XXVI), which is condensed with 2-chloroacetonitrile (XXVII) by means of K2CO3 in refluxing acetone to provide the precursor (XXVIII). Finally, the cyano group of (XXVIII) is hydrolyzed with KOH in refluxing water.

合成路线2

合成路线3