合成路线1

The esterification of L-malic acid (VII) with methanol in acidic medium gives the dimethyl ester (VIII), which is chemoselectively reduced with BH3, Me2S and NaBH4 yielding the diol (IX). The reaction of (IX) with trimethyl orthoformate affords the cyclic orthoester (X), which is reduced with DIBAL to the aldehyde (XI). The methylation of (XI) with MeLi provides the isopropanol derivative (XII), which is submitted to a Swern oxidation to afford the corresponding ketone (XIII). The enolization of (XIII) with TBDMS-OTf and DIEA gives the silylated enol ether (XIV), which is finally cyclized to the target ketone (IV) by means of Lewis acids such as TiCl4, BF3.Et2O, SnCl4 or Et2AlCl, the best yields being obtained with the last mentioned reagent.