合成路线1

1) The condensation of 1-phenylhexan-3-one (I) with ethyl acetate by means of butyllithium and diisopropylamine in THF gives racemic 3-hydroxy-3-(2-phenylethyl)hexanoic acid ethyl ester (II), which is hydrolyzed with NaOH in methanol to the corresponding free acid (III). The optical resolution of (III) with (1R,2S)-(-)-norephedrine (IV) followed by treatment with aqueous HCl yields the chiral (R)-acid (V), which is treated with 4-biphenylyloxymethyl chloride (VI) and diisopropylethylamine in toluene affording the protected ester (VII). The reduction of the ester group of (VII) with diisobutylaluminum hydride (DIBAL) in toluene gives the monoprotected diol (VIII), which is oxidized at the primary hydroxy group with 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) and NaOCl yielding the corresponding aldehyde (IX). The condensation of (IX) with (R)-3-(3-nitrophenyl)pentanoic acid methyl ester (X) by means of sodium hexamethyldisilazide (NaHMDS) in THF gives the hydroxyester (XI) as a mixture of four diastereomers. This mixture is oxidized with pyridinium chlorochromate (PCC) in dichloromethane to afford the ketoester (XII) also as a mixture of two diastereomers. Elimination of the biphenylyloxymethyl protecting group with H2SO4 in methanol yields the hydroxy ketoester (XIII).

合成路线2