合成路线1

The reaction of the chiral propyl iodide (VIII) with KCN in hot DMF gives the chiral butyronitrile (IX), which is reduced with DIBAL in dichloromethane to yield the butyraldehyde (X). The reaction of (X) with CBr4, PPH3 and BuLi in THF/dichloromethane affords the chiral alkyne (XI), which is treated with Me3Al, Cp2ZrCl2 and BuLi in dichloroethane to provide the vinyl aluminate (XII). The condensation of (XII) with the chiral epoxide (XIII) in benzene gives the unsaturated 2-octenol (XIV), which is protected with BnBr and NaH to yield the benzyl ether (XV). The desilylation of (XV) by means of TBAF in THF afford the primary alcohol (XVI), which is treated with diphenyl disulfide and Bu3P in DMF to provide the thioether (XVII). The oxidation of (XVII) with oxone in THF/methanol/water gives the corresponding sulfone (XVIII), which is condensed with the intermediate desired tetrahydropyran-carboxylic acid methyl ester (VII) by means of BuLi in THF to yield the adduct (XIX). The removal of the sulfone group of (XIX) is performed by means of Bu3SnH and AIBN in refluxing toluene affording the ketonic intermediate (XX).