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【结 构 式】 
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【分子编号】26118 【品名】tert-butyl[2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]dimethylsilane; tert-butyl(dimethyl)silyl 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl ether 【CA登记号】 |
【 分 子 式 】C24H34O5Si 【 分 子 量 】430.61646 【元素组成】C 66.94% H 7.96% O 18.58% Si 6.52% |
合成路线1
该中间体在本合成路线中的序号：(IV)The CH2Cl2/MeOH extracts of Combretum caffrum stem wood were fractionated using a solvent partition sequence, followed by gel filtration and column chromatography to provide a mixture of three substituted stilbenes: combretastatin A-4 (I), combretastatin A-5 (II) and combretastatin A-6 (III). Further separation of these compounds was achieved via derivatization with tert-butyldimethylsilyl chloride and separation of the respective silyl ethers (IV), (V) and (VI) by preparative TLC. The least polar component (IV) was then desilylated by treatment with tetrabutylammonium fluoride to yield pure combretastatin A-4 (I)
| 【1】 Pettit, G.R.; Singh, S.B.; Boyd, M.R.; Hamel, E.; Pettit, R.K.; Schmidt, J.M.; Hogan, F.; Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6. J Med Chem 1995, 38, 10, 1666. |
| 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) | 60505 | 2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol | 117048-60-9 | C18H20O5 | 详情 | 详情 |
| (II) | 60506 | 5-[(Z)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenol | C18H20O5 | 详情 | 详情 | |
| (III) | 65172 | 5-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenol | C18H20O5 | 详情 | 详情 | |
| (IV) | 26118 | tert-butyl[2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]dimethylsilane; tert-butyl(dimethyl)silyl 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl ether | C24H34O5Si | 详情 | 详情 | |
| (V) | 60507 | tert-butyl(dimethyl)silyl 5-[(Z)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenyl ether; tert-butyl{5-[(Z)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenoxy}dimethylsilane | C24H34O5Si | 详情 | 详情 | |
| (VI) | 65173 | tert-butyl{5-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenoxy}dimethylsilane; tert-butyl(dimethyl)silyl 5-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-2,3-dimethoxyphenyl ether | C24H34O5Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The O-silyl stilbene precursor (IV) was also synthesized by the Wittig reaction either between 3,4,5-trimethoxybenzaldehyde (VII) and the phosphonium salt (VIII) or between phosphonium bromide (IX) and 3-(tert-butyldimethylsilyloxy)-4-methoxybenzaldehyde (X), to furnish in both cases a mixture of the target Z-stilbene (IV) and its E-isomer (XI), which were separated by flash chromatography
| 【1】 Pettit, G.R.; Singh, S.B.; Boyd, M.R.; Hamel, E.; Pettit, R.K.; Schmidt, J.M.; Hogan, F.; Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6. J Med Chem 1995, 38, 10, 1666. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 26118 | tert-butyl[2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]dimethylsilane; tert-butyl(dimethyl)silyl 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl ether | C24H34O5Si | 详情 | 详情 | |
| (VII) | 11136 | 3,4,5-Trimethoxybenzaldehyde | 86-81-7 | C10H12O4 | 详情 | 详情 |
| (VIII) | 26117 | (3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzyl)(triphenyl)phosphonium bromide | C32H38BrO2PSi | 详情 | 详情 | |
| (IX) | 19866 | triphenyl(3,4,5-trimethoxybenzyl)phosphonium bromide | C28H28BrO3P | 详情 | 详情 | |
| (X) | 26114 | 3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzaldehyde | C14H22O3Si | 详情 | 详情 | |
| (XI) | 60508 | tert-butyl{2-methoxy-4-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy}dimethylsilane; tert-butyl(dimethyl)silyl 2-methoxy-4-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl ether | C24H34O5Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)Isovanillin (I) was protected as the silyl ether (II) and subsequently reduced to the benzyl alcohol (III). After conversion of (III) to bromide (IV), its reaction with triphenylphosphine gave phosphonium bromide (V). The ylide resulting from deprotonation of (V) with n-butyllithium was then condensed with 3,4,5-trimethoxybenzaldehyde (VI) to afford the required E-stilbene (VII) along with the corresponding Z-isomer, which were separated by column chromatography. Asymmetric Sharpless dihydroxylation of (VII) by means of AD mix-alpha provided the (1S,2S)-diol (VIII). Finally, desilylation of (VIII) using tetrabutylammonium fluoride afforded the target phenol.
| 【1】 Pettit, G.R.; Singh, S.B.; Boyd, M.R.; Hamel, E.; Pettit, R.K.; Schmidt, J.M.; Hogan, F.; Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6. J Med Chem 1995, 38, 10, 1666. |
| 【2】 Pettit, G.R.; et al.; Antineoplastic agents. 410. Asymmetric hydroxylation of trans-combretastatin A-4. J Med Chem 1999, 42, 8, 1459. |
| 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) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
| (II) | 26114 | 3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzaldehyde | C14H22O3Si | 详情 | 详情 | |
| (III) | 26115 | (3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxyphenyl)methanol | C14H24O3Si | 详情 | 详情 | |
| (IV) | 26116 | 4-(bromomethyl)-2-[[tert-butyl(dimethyl)silyl]oxy]phenyl methyl ether; [5-(bromomethyl)-2-methoxyphenoxy](tert-butyl)dimethylsilane | C14H23BrO2Si | 详情 | 详情 | |
| (V) | 26117 | (3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxybenzyl)(triphenyl)phosphonium bromide | C32H38BrO2PSi | 详情 | 详情 | |
| (VI) | 11136 | 3,4,5-Trimethoxybenzaldehyde | 86-81-7 | C10H12O4 | 详情 | 详情 |
| (VII) | 26118 | tert-butyl[2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]dimethylsilane; tert-butyl(dimethyl)silyl 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl ether | C24H34O5Si | 详情 | 详情 | |
| (VIII) | 26119 | (1S,2S)-1-(3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-1,2-ethanediol | C24H36O7Si | 详情 | 详情 |