合成路线1

The dihydroxylation of 2-[3-(tert-butyldimethylsilyloxy)-1-propenyl]furan (I) with OsO4 and NMO gives the racemic diol (II), which is oxidized with MCPBA to yield the dhydropyranone (III). The cyclization of (III) by means of Ts-OH affords the racemic bicyclic enone (IV), which is reduced with NaBH4 to the racemic alcohol (V). The reaction of (V) with Ac2O and pyridine provides the racemic acetate (VI), which is treated with Lipase PS and vinyl acetate, furnishing a mixture of unreacted chiral acetate (-)-(VI) and the chiral alcohol (+)-(VII), which are easily separated. The reduction of (-)-(VII) with H2 over PtO2 gives the bicyclic alcohol (VIII), which is treated with Ms-Cl and TEA to yield the mesylate (IX). The reaction of (IX) with sodium azide in THF affords the azido derivative (X), which is reduced with LiAlH4 in THF to provide the bicyclic amine (XI). The protection of (XI) with benzyl chloroformate gives the carbamate (XII), which is alkylated with allyl bromide (XIII) and NaH in DMF to yield the N-allyl carbamate (XIV). The desilylation of (XIV) with TBAF, followed by a treatment with Ms-Cl and TEA, affords the mesylate (XV). The reaction of (XV) with LiI, and then reaction of the intermediate iodide with Zn/HOAc, provides the hemiacetal (XVI), which is further reduced with NaBH4 in ethanol to give the dihydroxydiene (XVII). The ring-closing metathesis reaction of (XVII) by means of Grubbs' catalyst yields the tetrahydropyridine (XVIII), which is reduced with H2 over PtO2 to afford the chiral dihydroxy piperidine (XIX). The reaction of (XIX) with diphenyl disulfide and tributyl phosphine provides the thioether (XX), which is treated with benzyl bromide and NaH to give the piperidin benzyl ether (XXI).