合成路线1

Enantioselective cycloaddition of dienyne (XVII) with aldehyde (XVIII) affords dihydropyran (XIX). Subsequent Rubottom oxidation of the silyl enol ether (XIX) gives a mixture of epimeric alpha-hydroxy ketones (XX), which is further equilibrated to the desired stereoisomer (XXI) in the presence of K2CO3 in MeOH. After protection of the hydroxyl group of (XXI) as the triisopropylsilyl ether (XXII), Wittig reaction with methylene triphenylphosphorane provides the exocyclic olefin (XXIII). Replacement of the silylated primary hydroxyl of (XXIII) with a iodide group to yield (XXIV) is accomplished by treatment with I2 and PPh3. Removal of the remaining silyl group of (XXIV) with tetrabutylammonium fluoride and acetic acid yields the allylic alcohol (XXV), which can be diastereoselectively epoxidized with t butyl hydroperoxide and vanadyl acetylacetonate, producing (XXVI) as a single isomer. Reprotection of (XXVI) with triisopropylsilyl triflate affords the corresponding silyl ether (XXVII). Hydrozirconation of acetylene (XXVII), followed by Negishi coupling with the vinyl iodide (XVI) furnishes the diene system (XXVIII). Subsequent azido group reduction in (XXVIII) with trimethylphosphine in moist THF provides amine (XXIX).