Irisquinone A, Irisquinone, Iq-7611, -Drug Synthesis Database

【结构式】

【药物名称】Irisquinone A, Irisquinone, Iq-7611

【化学名称】2-[10(Z)-Heptadecenyl]-6-methoxy-1,4-benzoquinone

【CA登记号】56495-82-0

【分子式】C₂₄H₃₈O₃

【分子量】374.56866

【开发单位】Shandong Xinghua (Originator), Shanghai Inst. Pharm. Ind. (Originator), Tianjin Institute of Materia Medica (Originator)

【药理作用】ONCOLYTIC DRUGS, Radiation Therapy, Radiosensitizers

合成路线1 合成路线2 合成路线3

合成路线1

Irisquinone was originally isolated from some Iris species. The total synthesis of this compound has been reported by several procedures. 10-cis-Heptadecenoic acid (I) was converted to the Weinreb amide (II) via the corresponding acid chloride. Regiospecific ortho-lithiation of veratrole (III), followed by acylation with the N-methoxy amide (II), afforded ketone (IV). Selective mono-demethylation of (IV) with boron trichloride yielded phenol (V). Clemmensen reduction of the keto group of (V) employing zinc amalgam furnished 2-(cis-10-heptadecenyl)-6-methoxyphenol (VI). This was finally oxidized to the target quinone by means of oxygen gas in the presence of salcomine.

参考文献中间体

【1】 Haugwitz, R.D.; Risbood, P.A.; Parsons, J.L.; Myers, D.R.; Michalak, R.S.; Narayanan, V.L.; The synthesis of irisquinone. Tetrahedron Lett 1989, 30, 36, 4783.

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)	56670	cis-10-Heptadecenoic acid	29743-97-3	C₁₇H₃₂O₂	详情	详情
(II)	56671	(Z)-N-methoxy-N-methyl-10-heptadecenamide		C₁₉H₃₇NO₂	详情	详情
(III)	17395	1-(4-fluorophenethyl)-4-piperidinecarboxamide		C₁₄H₁₉FN₂O	详情	详情
(IV)	56672	(Z)-1-(2,3-dimethoxyphenyl)-10-heptadecen-1-one		C₂₅H₄₀O₃	详情	详情
(V)	56673	(Z)-1-(2-hydroxy-3-methoxyphenyl)-10-heptadecen-1-one		C₂₄H₃₈O₃	详情	详情
(VI)	56674	2-[(Z)-10-heptadecenyl]-6-methoxyphenol		C₂₄H₄₀O₂	详情	详情

合成路线2

In a different strategy, 3-methoxysalicylaldehyde (VII) was protected as the silyl ether (VIII) using t-butyldimethylsilyl chloride and Et3N. Wittig reaction of aldehyde (VIII) with (9-hydroxynonyl)triphenylphosphonium bromide (IX) afforded olefin (X). This was alternatively prepared by addition of Grignard reagent (XI) to the aldehyde (VIII) to give carbinol (XII), which was further subjected to dehydration and acetal hydrolysis under acidic conditions to afford (X). Catalytic hydrogenation of olefin (X) furnished the 10-aryl decanol (XIII). The heptadecenyl side chain of (XVI) was then constructed by Swern oxidation of alcohol (XIII) to the corresponding aldehyde (XIV), followed by Wittig reaction with heptyltriphenylphosphonium bromide (XV). Desilylation of (XVI) with tetrabutylammonium fluoride gave the phenol precursor (VI), which was finally oxidized to the desired quinone by the same method as above.

参考文献中间体

【1】 Wu, S.J.; Yang, Q.Z.; Chemical studies of Iris pallasii Fisch. var. chinensis Fisch.. Acta Chim Sin 1980, 38, 2, 156.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	56674	2-[(Z)-10-heptadecenyl]-6-methoxyphenol		C₂₄H₄₀O₂	详情	详情
(VII)	12620	o-Vanillin; 2-Hydroxy-3-methoxybenzaldehyde	148-53-8	C₈H₈O₃	详情	详情
(VIII)	56675	2-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxybenzaldehyde		C₁₄H₂₂O₃Si	详情	详情
(IX)	56676	(9-hydroxynonyl)(triphenyl)phosphonium bromide		C₂₇H₃₄BrOP	详情	详情
(X)	56677	(Z)-10-(2-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxyphenyl)-9-decen-1-ol		C₂₃H₄₀O₃Si	详情	详情
(XI)	56678	bromo[9-(1-ethoxyethoxy)nonyl]magnesium		C₁₃H₂₇BrMgO₂	详情	详情
(XII)	56679	1-(2-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxyphenyl)-10-(1-ethoxyethoxy)-1-decanol		C₂₇H₅₀O₅Si	详情	详情
(XIII)	56680	10-(2-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxyphenyl)-1-decanol		C₂₃H₄₂O₃Si	详情	详情
(XIV)	56681	10-(2-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxyphenyl)decanal		C₂₃H₄₀O₃Si	详情	详情
(XV)	56682	heptyl(triphenyl)phosphonium bromide	13423-48-8	C₂₅H₃₀BrP	详情	详情
(XVI)	56683	tert-butyl{2-[(Z)-10-heptadecenyl]-6-methoxyphenoxy}dimethylsilane; tert-butyl(dimethyl)silyl 2-[(Z)-10-heptadecenyl]-6-methoxyphenyl ether		C₃₀H₅₄O₂Si	详情	详情

合成路线3

Alternatively, the bis-methoxymethyl ether (XVIII), prepared from 2-bromo-6-methoxyhydroquinone (XVII), was subjected to palladium-catalyzed coupling with 9-decen-1-ol (XIX) to afford adduct (XX). After catalytic hydrogenation of olefin (XX), the resultant saturated alcohol (XXI) was oxidized to aldehyde (XXII) under Swern conditions. Wittig condensation of (XXII) with the phosphonium salt (XV) led to the heptadecenyl derivative (XXIII). Subsequent hydrolysis of the methoxymethyl ethers of (XXIII) by means of HBr in EtOH furnished the deprotected hydroquinone (XXIV). This was finally oxidized to the title quinone employing silver carbonate in benzene.

参考文献中间体

【1】 Yadav, J.S.; et al.; A practical preparation of functionalized alkylbenzoquinones synthesis of maesanin and irisquinone. J Org Chem 1992, 57, 11, 3242.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	56682	heptyl(triphenyl)phosphonium bromide	13423-48-8	C₂₅H₃₀BrP	详情	详情
(XVII)	56684	2-bromo-6-methoxy-1,4-benzenediol		C₇H₇BrO₃	详情	详情
(XVIII)	56685	1-bromo-3-methoxy-2,5-bis(methoxymethoxy)benzene; 3-bromo-2,5-bis(methoxymethoxy)phenyl methyl ether		C₁₁H₁₅BrO₅	详情	详情
(XIX)	56686	9-Decen-1-ol; 9-Decene-1-ol; omega-Decen-1-ol; Trepanol; Decylenic alcohol	13019-22-2	C₁₀H₂₀O	详情	详情
(XX)	56687	(E)-10-[3-methoxy-2,5-bis(methoxymethoxy)phenyl]-9-decen-1-ol		C₂₁H₃₄O₆	详情	详情
(XXI)	56688	10-[3-methoxy-2,5-bis(methoxymethoxy)phenyl]-1-decanol		C₂₁H₃₆O₆	详情	详情
(XXII)	56689	10-[3-methoxy-2,5-bis(methoxymethoxy)phenyl]decanal		C₂₁H₃₄O₆	详情	详情
(XXIII)	56690	3-[(Z)-10-heptadecenyl]-2,5-bis(methoxymethoxy)phenyl methyl ether; 1-[(Z)-10-heptadecenyl]-3-methoxy-2,5-bis(methoxymethoxy)benzene		C₂₈H₄₈O₅	详情	详情
(XXIV)	56691	2-[(Z)-10-heptadecenyl]-6-methoxy-1,4-benzenediol		C₂₄H₄₀O₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)