Gossypol, -Drug Synthesis Database

【结构式】

【药物名称】Gossypol

【化学名称】1,1',6,6',7,7'-Hexahydroxy-3,3'-dimethyl-5,5'-diisopropyl-(2,2'-binaphthalene)-8,8'-dicarboxaldehyde
　　　　　　2,2'-Bis(1,6,7-trihydroxy-3-methyl-5-isopropyl-8-formylnaphthalene)

【CA登记号】303-45-7

【分子式】C₃₀H₃₀O₈

【分子量】518.5688

【开发单位】Xian Lijun Pharmaceutical (Originator), Bioenvision (Licensee)

【药理作用】Bladder Cancer Therapy , Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Male Contraceptives, Oncolytic Drugs, Prostate Cancer Therapy, Antimitotic Drugs, bcl-xl Inhibitors, Steroid 5alpha-Reductase Inhibitors

合成路线1 合成路线2

合成路线1

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).

参考文献中间体

【1】 Cashaw, J.L.; Edwards, J.D.Jr.; Studies in the naphtalene series. III. Synthesis of apogossypol hexamethyl ether. J Am Chem Soc 1957, 79, 2283.
【2】 Edwards, J.D.Jr.; Total synthesis of gossypol. J Am Chem Soc 1958, 80, 3798.
【3】 El-Nockrashy; J Am Oil Chem Soc 1963, 40, 1, 14.
【4】 Leeson, P.; Gossypol. Drugs Fut 1979, 4, 5, 338.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	33240	2-isopropyl-3,4-dimethoxybenzaldehyde		C₁₂H₁₆O₃	详情	详情
(II)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(III)	33241	(E)-3-(ethoxycarbonyl)-4-(2-isopropyl-3,4-dimethoxyphenyl)-3-butenoic acid		C₁₈H₂₄O₆	详情	详情
(IV)	33242	4-hydroxy-8-isopropyl-6,7-dimethoxy-2-naphthoic acid		C₁₆H₁₈O₅	详情	详情
(V)	33243	3-(hydroxymethyl)-5-isopropyl-6,7-dimethoxy-1-naphthol		C₁₆H₂₀O₄	详情	详情
(VI)	33244	5-isopropyl-6,7-dimethoxy-3-methyl-1-naphthol		C₁₆H₂₀O₃	详情	详情
(VII)	33245	2-(1-hydroxy-5-isopropyl-6,7-dimethoxy-3-methyl-2-naphthyl)-5-isopropyl-6,7-dimethoxy-3-methyl-1-naphthol		C₃₂H₃₈O₆	详情	详情

合成路线2

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.

参考文献中间体

【1】 Cashaw, J.L.; Edwards, J.D.Jr.; Studies in the naphtalene series. III. Synthesis of apogossypol hexamethyl ether. J Am Chem Soc 1957, 79, 2283.
【2】 Edwards, J.D.Jr.; Total synthesis of gossypol. J Am Chem Soc 1958, 80, 3798.
【3】 El-Nockrashy; J Am Oil Chem Soc 1963, 40, 1, 14.
【4】 Leeson, P.; Gossypol. Drugs Fut 1979, 4, 5, 338.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	33245	2-(1-hydroxy-5-isopropyl-6,7-dimethoxy-3-methyl-2-naphthyl)-5-isopropyl-6,7-dimethoxy-3-methyl-1-naphthol		C₃₂H₃₈O₆	详情	详情
(VIII)	33246	1-isopropyl-6-(5-isopropyl-1,6,7-trimethoxy-3-methyl-2-naphthyl)-2,3,5-trimethoxy-7-methylnaphthalene; 1-isopropyl-6-(5-isopropyl-1,6,7-trimethoxy-3-methyl-2-naphthyl)-3,5-dimethoxy-7-methyl-2-naphthyl methyl ether		C₃₄H₄₂O₆	详情	详情
(IX)	33247	5-isopropyl-3-methyl-2-(1,6,7-trihydroxy-5-isopropyl-3-methyl-2-naphthyl)-1,6,7-naphthalenetriol		C₂₈H₃₀O₆	详情	详情
(X)	33248	N,N'-diphenyliminoformamide	622-15-1	C₁₃H₁₂N₂	详情	详情
(XI)	33249	5-isopropyl-3-methyl-8-[(phenylimino)methyl]-2-[1,6,7-trihydroxy-5-isopropyl-3-methyl-8-[(phenylimino)methyl]-2-naphthyl]-1,6,7-naphthalenetriol		C₄₂H₄₀N₂O₆	详情	详情

Extended Information