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【结 构 式】 
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【药物名称】Resveratrol, trans-Resveratrol, SRT501, 184072 【化学名称】3,4',5-Trihydroxy-trans-stilbene 【CA登记号】501-36-0 【 分 子 式 】C14H12O3 【 分 子 量 】228.24994 |
【开发单位】National Cancer Institute (Not Determined) 【药理作用】Anti-Herpes Virus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs, CARDIOVASCULAR DRUGS, Chemoprotective Agents, ONCOLYTIC DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Apoptosis Inducers, Cyclooxygenase-1 Inhibitors, Lipid Peroxidation Inhibitors |
合成路线1
The reaction of 3,5-dihydroxybenzoic acid (I) with Bn-Br, K2CO3 and 18-crown-6 in refluxing acetone gives 3,5-bis(benzyloxy)benzoic acid (II), which is reduced with LiAlH4 in ethyl ether to yield the corresponding benzyl alcohol (III). The reaction of (III) with PBr3 in ethyl ether/pyridine affords the benzyl bromide (IV), which is treated with triisopropyl phosphite (V) at 140-150 C to provide the phosphonate (VI). The condensation of (VI) with 4-benzyloxybenzaldehyde (VII) by means of NaOMe in DMF gives (E)-3,4',5-tris(benzyloxy)stilbene (VIII), which is finally debenzylated by treatment with BBr3 in dichloromethane. Alternatively, the synthesis of the target product can be performed by first condensation of 3,5-dimethoxybenzoyl chloride (IX) with 4-acetoxystyrene (X) by means of palladium(II) acetate and Et3N in p-xylene to yield (E)-4-acetoxy-3',5'-dimethoxystilbene (XI), whose acetoxy group is subjected to saponification either with NaOMe or with K2CO3 in THF/H2O/MeOH and whose methoxy groups are cleaved by means of BBr3 in CH2Cl2.
| 【1】 Meredith, E.; Andrus, M. (Brigham Young University); Synthesis of resveratrol. WO 0160774 . |
| 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) | 16230 | resorcylic acid; 3,5-dihydroxybenzoic acid | 99-10-5 | C7H6O4 | 详情 | 详情 |
| (II) | 25157 | 3,5-bis(benzyloxy)benzoic acid | 28917-43-3 | C21H18O4 | 详情 | 详情 |
| (III) | 50091 | [3,5-bis(benzyloxy)phenyl]methanol | C21H20O3 | 详情 | 详情 | |
| (IV) | 50092 | 1,3-bis(benzyloxy)-5-(bromomethyl)benzene; benzyl 3-(benzyloxy)-5-(bromomethyl)phenyl ether | C21H19BrO2 | 详情 | 详情 | |
| (V) | 32162 | Triisopropyl phosphite | 116-17-6 | C9H21O3P | 详情 | 详情 |
| (VI) | 50093 | diisopropyl 3,5-bis(benzyloxy)benzylphosphonate | C27H33O5P | 详情 | 详情 | |
| (VII) | 29179 | 4-(Benzyloxy)benzaldehyde | 4397-53-9 | C14H12O2 | 详情 | 详情 |
| (VIII) | 50094 | benzyl 3-(benzyloxy)-5-[(E)-2-[4-(benzyloxy)phenyl]ethenyl]phenyl ether; 1,3-bis(benzyloxy)-5-[(E)-2-[4-(benzyloxy)phenyl]ethenyl]benzene | C35H30O3 | 详情 | 详情 | |
| (IX) | 50095 | 3,5-Dimethoxybenzoyl chloride | 17213-57-9 | C9H9ClO3 | 详情 | 详情 |
| (X) | 27297 | 4-vinylphenyl acetate | 2628-16-2 | C10H10O2 | 详情 | 详情 |
| (XI) | 50096 | 4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl acetate | C18H18O4 | 详情 | 详情 |
合成路线2
The reaction of 3,5-dihydroxybenzaldehyde (I) with Tbdms-Cl gives the disilylated aldehyde (II), which by a Wittig condensation with methylenetriphenylphosphorane (III) yields the 3,5-dihydroxystyrene (IV). The reaction of (IV) with acetic anhydride and pyridine affords 3,5-diacetoxystyrene (V), which was submitted to a Heck condensation with 4-acetoxyiodobenzene (VI) by means of Pd(OAc)2 and PPh3 in hot acetonitrile to provide 3,4',5-triacetopxy-(E)-stilbene (VII). Finally, this compound is deacetylated by means of NaOMe in THF/methanol to furnish the target resveratrol.
| 【1】 Guiso, M.; et al.; A new efficient resveratrol synthesis. Tetrahedron Lett 2002, 43, 4, 597. |
| 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) | 52215 | 3,5-Dihydroxybenzaldehyde | C7H6O3 | 详情 | 详情 | |
| (II) | 52216 | 3,5-bis{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde | C19H34O3Si2 | 详情 | 详情 | |
| (III) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 | |
| (IV) | 52217 | 5-vinyl-1,3-benzenediol | C8H8O2 | 详情 | 详情 | |
| (V) | 52218 | 3-(acetyloxy)-5-vinylphenyl acetate | C12H12O4 | 详情 | 详情 | |
| (VI) | 52219 | 4-iodophenyl acetate | C8H7IO2 | 详情 | 详情 | |
| (VII) | 52220 | 3-(acetyloxy)-5-{(E)-2-[4-(acetyloxy)phenyl]ethenyl}phenyl acetate | C20H18O6 | 详情 | 详情 |
合成路线3
The reaction of 4-methoxyphenyl iodide (I) with trimethylvinyllsilane (II) and 3,5-dimethoxyphenyl iodide (III) by means of Pd(dba)2, KF, tetrabutylammonium chloride (TBAC) and K2CO3 in toluene gives the trimethoxystilbene (IV), which is finally demethylated by reaction with BCl3 and tetrabutylammonium iodide (TBAI) in dichloromethane to afford the target Resveratrol.
| 【1】 Jeffery, T.; Ferber, B.; One-pot palladium-catalyzed highly chemo-, regio-, and stereoselective synthesis of trans-stilbene derivatives. A concise and convenient synthesis of resveratrol. Tetrahedron Lett 2003, 44, 1, 193. |
| 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) | 31009 | 1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether | 696-62-8 | C7H7IO | 详情 | 详情 |
| (II) | 62022 | Vinyltrimethylsilane; Ethenyltrimethylsilane; Trimethylvinylsilane; TRIMETHYL(VINYL)SILANE; (Trimethylsilyl)ethylene; Vinyltrimethylsilane; Vinyl-trimethylsilan; (Trimethylsilyl)ethylene; (ETHENYLTRIMETHYLSILANE, TRIMETHYLVINYLSILANE) | 754-05-2 | C5H12Si | 详情 | 详情 |
| (III) | 62023 | 3-iodo-5-methoxyphenyl methyl ether; 1-iodo-3,5-dimethoxybenzene | C8H9IO2 | 详情 | 详情 | |
| (IV) | 62024 | 4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl methyl ether; 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene | C17H18O3 | 详情 | 详情 |