合成路线1

The synthesis of the 1,3-dioxane intermediate (XIII) has been performed as follows: The reaction of 2(S)-hydroxycyclopentanone (I) with Tbdps-Cl and imidazole in DMF gives the silyl ether (II), which is condensed with the phosphonate (III) by means of BuLi in THF to yield the new phosphonate (IV) after silylation with Tes-Cl and LDA. The Horner-Wadsworth-Emmons olefination of carbaldehyde (V) with phosphonate (IV) by means of LiCl and TEA in THF affords the silylated ketone (VI), which is reduced with NaBH4/CeCl3 and protected with Mom-Cl and DIEA to provide the dihydropyran derivative (VII). The cleavage of the Tes protecting group by means of TsOH, followed by oxidation of the resulting alcohol with SO3/pyridine in DMSO/dichloromethane gives the aldehyde (VIII). A new olefination reaction of aldehyde (VIII) with phosphorane (IX) by means of NaH in THF yields the methoxyamide (X), which is reduced with DIBAL in THF to afford the unsaturated aldehyde (XI). Finally, this aldehyde is treated with (2R,4R)-pentanediol (XII) and montmorillonite K-10 in hot toluene to provide the target 1,3-dioxane intermediate (XIII).