合成路线1

8) Open form: The silylation of (S,S)-tartaric acid diisopropyl ester (LXI) with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF gives the bissilylated compound (LXII), which is condensed with the disodium salt of tert-butyl acetoacetate (LXIII) in THF, yielding (S,S)-7-(tert-butoxycarbonyl)-2,3-bis (tert-butyldimethylsilyloxy)-4,6-dioxoheptanoic acid isopropyl ester (LXIV). The selective reduction of (LXIV) with DIBAL in THF affords the monohydroxylated compound (LXV), which is further reduced with diethylmethoxyborane in THF to the dihydroxylated compound (LXVI). The protection of the OH groups of (LXVI) with 2,2-dimethoxypropane and p-toluenesulfonic acid gives the 1,3-dioxane derivative (LXVII), which is desilylated with TBAF in THF to the gem-diol (LXVIII). Oxidation of the diol (LXVIII) with sodium metaperiodate in water/ethyl ether affords the aldehyde (LXIX), which is then condensed with 2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-ylmethyl(diphenyl)phosphine oxide (LXX) by means of lithium 2,2,6,6-tetramethylpiperidine (TMPip-Li) or butyllithium in THF, giving the protected tert-butyl ester (XXII). Finally, this compound is deprotected and hydrolyzed with trifluoroacetic acid in dichloromethane. 9) The phosphine oxide (LXX) has been obtained as follows: 2-Cyclopropyl-4-(4-fluorophenyl)-3-(hydroxy-methyl)quinoline (LIX, Scheme 5) was treated with PBr3, yielding the corresponding bromomethyl derivative (LXXI), which was then treated with diphenyl(ethoxy)phosphorane in refluxing toluene.