合成路线1

The intermediate phenyl sulfone (XXIII) has been obtained as follows. The reaction of tetrahydropyranyl glycidol (I) with isopropenyl bromide (X) by means of CuCN in THF gives the secondary alcohol (XI), which is treated with allyl bromide (XII) and KH in THF to yield the allyl ether (XIII). A ring closing metathesis reaction with (XIII) catalyzed by a Ru catalyst yields the protected dihydropyran derivative (XIV), which is treated with CSA in methanol to afford the carbinol (XV). The oxidation of (XV) with (COCl)2 and DMSO in dichloromethane provides the carbaldehyde (XVI), which is treated with CBr4 and PPh3 in dichloromethane to give the dibromovinyl derivative (XVII). The condensation of (XVII) with the intermediate aldehyde (VI) by means of BuLi in THF yields the propargyl alcohol derivative (XVIII), which is oxidized with DMP to the corresponding acetylenic ketone (XIX). Alternatively, acetylenic ketone (XIX) can also be obtained by condensation of dibromovinyl derivative (XVII) with the intermediate Weinreb amide (IX) by means of BuLi in THF. The enantioselective reduction of ketone (XIX) with L-Selectride in THF affords the chiral propargyl alcohol (XX), which is reduced with Red-Al and treated with TFA to provide the trans-allylic alcohol (XXI). The reaction of the diol (XXI) with Pmp-CH(OEt)2 and CSA gives the acetal (XXII), which is finally reduced with DIBAL in dichloromethane to yield the intermediate Pmb-protected phenyl sulfone (XXIII).