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【结 构 式】 
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【药物名称】4, 6, 4'-Trimethylangelicin, TMA 【化学名称】4,6,9-Trimethyl-2H-furo[2,3-h]-1-benzopyran-2-one 【CA登记号】90370-29-9 【 分 子 式 】C14H12O3 【 分 子 量 】228.24994 |
【开发单位】Farmochimica (Originator) 【药理作用】Antipsoriatics, Dermatologic Drugs |
合成路线1
4,6-Dimethyl-7-acetylumbelliforone (4,6-dimethyl-7-acetoxycoumarin) (I) is submitted to the Fries' rearrangement, obtaining the 4,6-dimethyl-8-acetylumbelliferone (II); the latter (II) is condensed with ethylbromoacetate (A) and the resulting ethyl [(4,6-dimethyl-8-acetyl-7-coumarinyl)oxy]acetate (III) is hydrolyzed by refluxing with 5% KOH aqueous methanolic solution; from this solution, acidified with HCl, the [(4,6-dimethyl-8-acetyl-7-coumarinyl)oxy]acetic acid (IV) is extracted with EtOAc and purified by crystallization (EtOAc / n-hexane). Cyclization of (IV), carried out by refluxing in Ac2O in the presence of anhydrous natrium acetate, is accompanied by an almost complete decarboxylation of (V), yielding 4,6,4'-trimethylangelicin (TMA).
| 【1】 Guiotto, A.; et al.; 6-Methylangelicins: A new series of potential photochemotherapheutic agents for the treatment of psoriasis. J Med Chem 1984, 27, 8, 959. |
| 【2】 Bordin, F.; Dall'Acqua, F.; Cristofolini, M.; Guiotto, A.; 4,6,4'-Trimethylangelicin. Drugs Fut 1985, 10, 4, 307. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (I) | 29146 | 4,6-dimethyl-2-oxo-2H-chromen-7-yl acetate | C13H12O4 | 详情 | 详情 | |
| (II) | 29147 | 8-acetyl-7-hydroxy-4,6-dimethyl-2H-chromen-2-one | C13H12O4 | 详情 | 详情 | |
| (III) | 29148 | ethyl 2-[(8-acetyl-4,6-dimethyl-2-oxo-2H-chromen-7-yl)oxy]acetate | C17H18O6 | 详情 | 详情 | |
| (IV) | 29149 | 2-[(8-acetyl-4,6-dimethyl-2-oxo-2H-chromen-7-yl)oxy]acetic acid | C15H14O6 | 详情 | 详情 | |
| (V) | 29150 | 4,6,9-trimethyl-2-oxo-2H-furo[2,3-h]chromene-8-carboxylic acid | C15H12O5 | 详情 | 详情 |