The condensation of 3,4-dimethoxy-2-isopropylbenzaldehyde (I) with diethyl succinate (II) by means of NaH in refluxing benzene gives 2-(2-isopropyl-3,4-dimethoxybenzylidene)succinic acid monoethyl ester (III), which is cyclized by treatment with acetic anhydride and sodium acetate in refluxing acetic acid and hydrolyzed with NaOH in refluxing methanol yielding acid (IV). The reduction of (IV) with LiAlH4 in ether affords 3-hydroxymethyl-5-isopropyl-6,7-dimethoxy-1-naphthol (V), which is hydrogenated with H2 over Pd/C in methanol with some HCl giving 3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol (VI). Thermal dimerization of (VI) by heating at 215 C yields 2,2'-bis(3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol) (VII).

Intermediate (VII) is methylated with dimethylsulfate and KOH in refluxing aqueous dioxane affording apogossypol hexamethyl ether (VIII) . The cleavage of the methoxy groups with BBr3 and aqueous NaOH yields apogossypol (IX), which by reaction with N,N'-diphenylformamidine (X) affords gossypol bis(N-phenylimine) (XI), which is finally hydrolyzed.

The condensation of 3,4-dimethoxy-2-isopropylbenzaldehyde (I) with diethyl succinate (II) by means of NaH in refluxing benzene gives 2-(2-isopropyl-3,4-dimethoxybenzylidene)succinic acid monoethyl ester (III), which is cyclized by treatment with acetic anhydride and sodium acetate in refluxing acetic acid and hydrolyzed with NaOH in refluxing methanol yielding acid (IV). The reduction of (IV) with LiAlH4 in ether affords 3-hydroxymethyl-5-isopropyl-6,7-dimethoxy-1-naphthol (V), which is hydrogenated with H2 over Pd/C in methanol with some HCl giving 3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol (VI). Thermal dimerization of (VI) by heating at 215 C yields 2,2'-bis(3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol) (VII).

Intermediate (VII) is methylated with dimethylsulfate and KOH in refluxing aqueous dioxane affording apogossypol hexamethyl ether (VIII) . The cleavage of the methoxy groups with BBr3 and aqueous NaOH yields apogossypol (IX), which by reaction with N,N'-diphenylformamidine (X) affords gossypol bis(N-phenylimine) (XI), which is finally hydrolyzed.

The condensation of 3,4-dimethoxy-2-isopropylbenzaldehyde (I) with diethyl succinate (II) by means of NaH in refluxing benzene gives 2-(2-isopropyl-3,4-dimethoxybenzylidene)succinic acid monoethyl ester (III), which is cyclized by treatment with acetic anhydride and sodium acetate in refluxing acetic acid and hydrolyzed with NaOH in refluxing methanol yielding acid (IV). The reduction of (IV) with LiAlH4 in ether affords 3-hydroxymethyl-5-isopropyl-6,7-dimethoxy-1-naphthol (V), which is hydrogenated with H2 over Pd/C in methanol with some HCl giving 3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol (VI). Thermal dimerization of (VI) by heating at 215 C yields 2,2'-bis(3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol) (VII).

Intermediate (VII) is methylated with dimethylsulfate and KOH in refluxing aqueous dioxane affording apogossypol hexamethyl ether (VIII) . The cleavage of the methoxy groups with BBr3 and aqueous NaOH yields apogossypol (IX), which by reaction with N,N'-diphenylformamidine (X) affords gossypol bis(N-phenylimine) (XI), which is finally hydrolyzed.

The condensation of 3,4-dimethoxy-2-isopropylbenzaldehyde (I) with diethyl succinate (II) by means of NaH in refluxing benzene gives 2-(2-isopropyl-3,4-dimethoxybenzylidene)succinic acid monoethyl ester (III), which is cyclized by treatment with acetic anhydride and sodium acetate in refluxing acetic acid and hydrolyzed with NaOH in refluxing methanol yielding acid (IV). The reduction of (IV) with LiAlH4 in ether affords 3-hydroxymethyl-5-isopropyl-6,7-dimethoxy-1-naphthol (V), which is hydrogenated with H2 over Pd/C in methanol with some HCl giving 3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol (VI). Thermal dimerization of (VI) by heating at 215 C yields 2,2'-bis(3-methyl-5-isopropyl-6,7-dimethoxy-1-naphthol) (VII).

Intermediate (VII) is methylated with dimethylsulfate and KOH in refluxing aqueous dioxane affording apogossypol hexamethyl ether (VIII) . The cleavage of the methoxy groups with BBr3 and aqueous NaOH yields apogossypol (IX), which by reaction with N,N'-diphenylformamidine (X) affords gossypol bis(N-phenylimine) (XI), which is finally hydrolyzed.