合成路线1

The Grignard condensation of carbaldehyde (I) with methylmagnesium bromide in ethyl ether gives the secondary alcohol (II), which is oxidized with TPAP and NMO in dichloromethane to yield the methyl ketone (III). The aldol reaction of (III) with hexafluoroacetone (IV) by means of LiHMDS in THF affords the hexafluorohydroxy ketone (V), which is reduced with NaBH4 in THF/methanol to provide the diol (VI). The selective acetylation of the secondary OH group of (VI) with Ac2O and pyridine gives the monoacetate (VII), which is treated with Mom-Cl and DIEA in order to protect its tertiary OH group, yielding (VIII). The deacetylation of (VIII) with KOH in methanol affords the secondary alcohol (IX), which is treated with CS2, NaH and Me-I to provide the thionocarbonate (X). The reduction of (X) with Bu3SnH in refluxing toluene gives the protected intermediate (XI), which is finally deprotected by reaction with methanesulfonic acid in methanol to yield the target vitamin D3 derivative.