合成路线1

The enantioselective condensation of 2-bromovanillin (I) with cyclohexenecarboxylate (II) by means of the chiral phosphine ligand (III) gives the chiral aryl ether (IV), which is reduced with DIBAL to yield the diol (V). The protection of (V) with Tbdms-OTf affords the bis silyl ether (VI), which is cyclized by means of Pd(OAc)2 to furnish the tetrahydrodibenzofuran (VII). The deprotection of (VII) with TBAF gives the diol (VIII), which is chemoselectively oxidized with MnO2 to yield the hydroxyaldehyde (IX). The reductocondensation of (IX) with methylamine and NaBH3CN affords the secondary amine (X), which is protected with Boc2O, providing the carbamate (XI). The oxidation of (XI) with DMP gives the aldehyde (XII), which is condensed with the phosphonium bromide (XIII) and NaHMDS, yielding the vinyl ether (XIV). The deprotection and cyclization of (XIV) by means of TFA affords the seven-member ring hemiaminal (XV), which is reduced with NaBH3CN to provide deoxygalanthamine (XVI). The epoxidation of (XVI) with dimethyldioxirane (DMDO) and TsOH furnishes the epoxide (XVII), which is regioselectively opened with diphenyl diselenide and NaBH4 to give the alpha-hydroxy selenide (XVIII). Elimination of the selenide group of (XVIII) by oxidation with NaIO4 at 80 C yielded isogalanthamine (XIX), which is finally isomerized to the target compound by treatment with Osborn's rhenium catalyst (Ph3SiO-ReO3).