• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【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

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.

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.

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.

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