Friedel-Crafts condensation of 2-fluorobiphenyl (I) with glutaric anhydride (II) in the presence of AlCl3 gave ketoacid (III). Reduction of the ketonic group of (III) with triethylsilane in trifluoroacetic acid afforded biphenylpentanoic acid (IV), which was cyclized to the benzosuberone derivative (V) using polyphosphoric acid. Ketone reduction of (IV) by means of triethylsilane and trifluoroacetic acid provided the benzocycloheptene (VI), which was further oxidized to the isomeric ketone (VII) with chromic acid. Finally, condensation of (VII) with 5-fluoroisatin (VIII) in the presence of KOH yielded the target tetracyclic system.

Keto ester (III) was prepared by Friedel-Crafts acylation of 2-fluorobiphenyl (I) with methyl glutaryl chloride (II). Subsequent Pfitzinger condensation of (III) with 5-fluoroisatin (IV) furnished the quinoline derivative (V). Chlorination of diacid (V) with SOCl2, followed by treatment with methanol produced selectively the mono-ester (VI). The remaining carboxyl group of (VI) was activated with SOCl2 in the presence of DMF, and subsequently coupled with n-octyl amine to generate amide (VII). The methyl ester group of (VII) was then hydrolyzed to acid (VIII), which was further subjected to intramolecular ring closure upon heating with triflic acid to afford the tetracyclic system (IX). Keto group reduction in (IX) to give (X) was accomplished by a two-step procedure with NaBH4 and then with HI and Ac2O.

The title carboxylic acid was obtained by nitrosation of amide (X) with sodium nitrite and Ac2O, followed by treatment with KOH.

In a different strategy for protecting the quinoline carboxyl group, acid (VI) was reduced to alcohol (XI) via chlorination with SOCl2, followed by treatment with NaBH4. Alcohol (XI) was then converted to the alkyl chloride (XII) with SOCl2 in dichloroethane. Subsequent ester group hydrolysis in (XII) under acidic conditions furnished the carboxylic acid (XIII). The tetracyclic compound (XIV) was obtained by cyclization of acid (XIII) in hot triflic acid. Displacement of the chloride group of (XIV) with sodium acetate in HOAc yielded acetate ester (XV), which was subsequently hydrolyzed to alcohol (XVI). Oxidation of (XVI) with DMSO and Ac2O provided aldehyde (XVII).

Aldehyde (XVII) was further oxidized to carboxylic acid (XVIII) using sodium chlorite. Conversion of acid (XVIII) into the methyl ester (XIX) was effected by treatment with iodomethane and K2CO3. Finally, the two-step reduction of the carbonyl group of (XIX) with NaBH4 followed by HI/Ac2O, proceeded with concomitant ester hydrolysis, yielding the title compound.