合成路线1

The synthesis of the phosphonate intermediate (XXXVII) has been performed as follows: The reaction of the 2-hexynoic ester (XVIII) with Tbdps-Cl gives the silyl ether (XIX), which is reduced with DIBAL to yield the propargyl alcohol (XX). The protection of (XX) by reaction with dihydropyran affords the tetrahydropyranyl ether (XXI), which is selectively deprotected by means of DDQ to provide the acetylenic alcohol (XXII). The oxidation of (XXII) by means of SO3/pyridine, and NaClO2, followed by methylation with diazomethane gives the acetylenic ester (XXIII), which is condensed with phosphonate (XXIV) by means of BuLi to yield the chiral phosphonate (XXV). The condensation of (XXV) with 4-methyl-3,6-dihydro-2H-pyran-2(S)-carbaldehyde (XXVI) affords the ketonic adduct (XXVII), which is reduced with NaBH4 and CeCl3 to provide the secondary alcohol (XXVIII). The reaction of (XXVIII) with Mom-Cl gives the corresponding Mom-ether (XXIX), whose tetrahydropyranyl group is hydrolyzed by means of HCl to yield the primary alcohol (XXX). The selective monoreduction of the acetylenic triple bond of (XXX) by means of Red-Al affords the octadienyl alcohol (XXXI), which is oxidized with DMP to the expected aldehyde (XXXII). The reaction of (XXXII) with (R,R)-pentane-2,4-diol (XXXIII) affords the propylene ketal (XXXIV), which is desilylated by means of TBAF to provide the secondary alcohol (XXXV). The condensation of (XXXV) with the phosphonoacetic acid (XXXVI) furnishes the corresponding ester (XXXVII).