合成路线1

The cyclization of phosphonate (I) with the chiral alcohol (II) by means of tert-butyl hypochlorite and Et-MgBr gives the isoxazoline (III), which is condensed with 2-methylthiazole-4-carbaldehyde (IV) by means of DBU and LiCl in acetonitrile to yield the secondary alcohol (V). The oxidation of (V) with TPAP and NMO in dichloromethane affords the corresponding ketone (VI), which is treated with the Grignard reagent (VII) in THF to provide the expected secondary alcohol (VIII). The silylation of (VIII) with Tes-OTf in dichloromethane gives the silyl ether (IX), which is treated with SmI2, Et3B and NaBH4 to cleave the isoxazoline ring and yield the diol (X). The reaction of (X) with SOCl2, TEA and TBAF affords the chiral epoxide (XI), which is silylated with Tes-Cl and TEA to provide the silyl ether (XII). The selective hydrolysis of the primary silyl ether of (XII) with HOAc in THF/water gives the primary alcohol (XIII), which is oxidized with TPAP and NMO in dichloromethane to yield the corresponding aldehyde (XIV). The condensation of (XIV) with ketone (XV) by means of LDA affords the open-chain precursor (XVI).