合成路线1

A new synthesis of FTY-720 has been reported: Condensation of 4-chlorobenzaldehyde (I) with octylzinc iodide (II) by means of Ni(0) gives 4-octylbenzaldehyde (III), which is treated with vinylmagnesium bromide (IV) to yield the allyl alcohol (V). Epoxidation of (V) with MCPBA affords the epoxide (VI), which is opened by means of NaNO2 and MgSO4 in refluxing methanol to provide 3-nitro-1-(4-octylphenyl)propane-1,2-diol (VII). Reaction of diol (VII) with trimethylsilyl chloride and NaI in acetonitrile gives 3-nitro-1-(4-octylphenyl)-1-propene (VIII), which is hydrogenated with H2 over Pd/C in ethanol yielding the corresponding nitropropane derivative (IX). The bis-formylation of compound (IX) with aqueous HCHO in the presence of Amberlyst A-21 in dichloromethane affords 2-nitro-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (X), which is finally reduced with H2 over Ra-Ni to provide FTY-720.