合成路线1

The acetylenic ester intermediate (XVI) has been obtained as follows. The reaction of acetaldehyde (I) with acetyl bromide (II) by means of a chiral Al catalyst gives lactone (III), which is condensed with N,O-dimethylhydroxylamine (IV) to yield the Weinreb amide (V). The reduction of (V) with iBu2AlH affords the chiral butyraldehyde (VI), which is condensed with acetyl bromide (II) and DIEA to provide the lactone (VII). The reaction of (VII) with methylmagnesium bromide gives the chiral pentanoic acid (VIII), which is reduced with BH3/Me2S and reoxidated with PCC to yield the aldehyde (IX). The condensation of (IX) with acetyl bromide (II) and DIEA affords the lactone (X), which is treated with the lithium salt (XI) to provide the dihydropyranone (XII). The reduction of (XII) with NaBH4 and CeCl3, followed by reaction with Ac2O and TEA gives the acetoxy derivative (XIII), which is desilylated with TBAF and oxidized with PDC to yield the methyl ketone (XIV). Finally, the condensation of (XIV) with the allenic tributyl tin derivative (XV) by means of Bu3Sn-OTf in dichloromethane affords the target acetylenic ester intermediate (XVI).