合成路线1

The intermediates (I) and (II) are synthesized as follows: Intermediate (I): The carboxylic acid (VIII) is condensed with N-methoxy-N-methylamine by means of dicyclohexylcarbodiimide (DCC) in dichloromethane to the amide (IX), which is treated with the vinyl iodide (X) and butyllithium in ethyl ether to yield the ketone (XI). The reduction of (XI) with LiAlH4 followed by methylation with MeI and NaH in DMF affords the methoxy compound (XII), which by treatment with camphorsulfonic acid (CSA), triethylamine and K2CO3 in methanol is converted to the epoxide (XIII). The condensation of (XIII) with the iodo ether (XIV) by means of butyllithium followed by silylation with triisopropylsilyl trifluoromethanesulfonate in dichloromethane and iodination with N-iodosuccinimide (NIS) in THF gives the protected triol (XV), which is selectively oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and oxalyl chloride in DMSO/dichloromethane, yielding the aldehyde (XVI). The condensation of (XVI) with the oxazolidinone (XVII) by means of tributylboron trifluoromethanesulfonate in toluene/dichloromethane affords compound (XVIII), which is treated with LiOH and H2O2 in THF/water. The resulting free acid is methylated with diazomethane, and the free hydroxyl group is acetylated with acetic anhydride to the acetoxy ester (XIX). Finally, (XIX) is hydrolyzed with LiOH in methanol/water to afford intermediate (I) (see A.D. Piscopio et al., J Chem Soc Chem Commun 1993, 7: 617). (1,2)