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【结 构 式】 
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【药物名称】 【化学名称】(1S,2S)-1-(3-Hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane-1,2-diol 【CA登记号】 【 分 子 式 】C18H22O7 【 分 子 量 】350.37184 |
【开发单位】Arizona State University (Originator), National Cancer Institute (Codevelopment) 【药理作用】ONCOLYTIC DRUGS, Antimitotic Drugs, Microtubule-Stabilizing Agents |
合成路线1
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 |