合成路线1

The condensation of 3-(4-fluorophenyl)-2-(hydroxymethyl)-1-isopropyl-1H-indole (IX) with trimethyl phosphite by means of oxalyl chloride in toluene gives 3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-ylmethylphosphonic acid dimethyl ester (X), which is condensed with erythro-3,5-di(tert-butyldiphenylsilyloxy)-6-oxohexanoic acid allyl ester (XI) by means of butyllithium in THF yielding erythro-3,5-di(tert-butyldiphenylsilyloxy)-7-[3-(4-fluorophenyl)-1H-indol-2-yl]-6(E)-heptenoic acid allyl ester (XII). The hydrolysis of (XII) by means of triphenylphosphine and palladium tetrakis triphenylphosphine in acetic acid affords the corresponding silylated free acid (XIII), which is finally deprotected with tetrabutylammonium fluoride in THF - acetic acid, and treated with NaOH. (racemic). The allyl ester (XI) is obtained as follows: The hydrogenation of fluoroglucinol (XIV) with H2 over W4 Raney Nickel in ethanol gives, after crystallization, cis-1,3,5-trihydroxycyclohexane (XV), which is treated with tert-butyldiphenylsilyl chloride and imidazole in DMF to afford the bis-silylated compound (XVI). The oxidation of (XVI) with pyridinium chlorochromate in dichloromethane gives the protected cyclohexanone (XVII), which is oxidized again with m-chloroperbenzoic acid in dichloromethane yielding cis-4,6-bis(tert-butyldiphenylsilyloxy hexahydrooxepin-2-one (XVIII). The hydrolysis of (XVIII) with trifluoroacetic acid and refluxing allyl alcohol affords erythro-3,5-bis(tert-butyldiphenylsilyloxy)-6-hydroxyhexanoic acid allyl ester (XIX), which is finally oxidized with pyridinium chlorochromate in dichloromethane to give the desired oxo-ester (XI).