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【结 构 式】 
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【药物名称】Calothrixin B 【化学名称】12,13-Dihydro-7H-indolo[3,2-j]phenanthridine-7,13-dione 【CA登记号】254114-34-6 【 分 子 式 】C19H10N2O2 【 分 子 量 】298.30375 |
【开发单位】Australian National University (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Oncolytic Drugs, Treatment of Protozoal Diseases |
合成路线1
On the other hand, the synthesis of benzhydrylpyridazinone (X) is performed as follows: condensation of 1,1-diphenyl acetone (VII) with glyoxylic acid (VIII) in refluxing 1,2-dimethoxyethane yields oxopentanoic acid (IX), which is finally subjected to cyclization with hydrazine in refluxing H2O.
| 【1】 Kelly, T.R.; et al.; Synthesis of the potent antimalarials calothrixin A and B. Org Lett 2000, 2, 23, 3735. |
| 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) | 46797 | Indole-3-aldehyde; 3-Formylindole; 1H-Indole-3-carbaldehyde; Indole-3-carboxaldehyde | 487-89-8 | C9H7NO | 详情 | 详情 |
| (II) | 46798 | 1-(methoxymethyl)-1H-indole-3-carbaldehyde | C11H11NO2 | 详情 | 详情 | |
| (III) | 45801 | 4-quinolinecarboxylic acid | 486-74-8 | C10H7NO2 | 详情 | 详情 |
| (IV) | 46799 | N,N-diethyl-4-quinolinecarboxamide | C14H16N2O | 详情 | 详情 | |
| (V) | 46800 | 12-(methoxymethyl)-7H-indolo[3,2-j]phenanthridine-7,13(12H)-dione | C21H14N2O3 | 详情 | 详情 |
合成路线2
The methanolysis of anhydride (I) with dry refluxing methanol gives the monoester (II), which is treated with COCl2 to yield the acyl chloride (III). The condensation of (III) with indole (IV) by means of ZnCl2/MeMgCl and AlCl3 affords the adduct (V), which is N protected by means of Mom-Cl and NaH in THF to provide the intermediate (VI). The cyclization of (VI) by means of Temda and LiHMDS in THF gives the tetracyclic quinone (VII), which is finally deprotected with hot aq. HCl to provide the target Calothrixin B.
| 【1】 Bernardo, P.H.; et al.; A simple and concise route to calothrixin B. Tetrahedron Lett 2002, 43, 16, 2939. |
| 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) | 56959 | furo[3,4-c]quinoline-1,3-dione | C11H5NO3 | 详情 | 详情 | |
| (II) | 56960 | 4-(methoxycarbonyl)-3-quinolinecarboxylic acid | C12H9NO4 | 详情 | 详情 | |
| (III) | 56961 | methyl 3-(chlorocarbonyl)-4-quinolinecarboxylate | C12H8ClNO3 | 详情 | 详情 | |
| (IV) | 15292 | Indole; 1H-indole | 120-72-9 | C8H7N | 详情 | 详情 |
| (V) | 56962 | methyl 3-(1H-indol-3-ylcarbonyl)-4-quinolinecarboxylate | C20H14N2O3 | 详情 | 详情 | |
| (VI) | 56963 | methyl 3-{[1-(methoxymethyl)-1H-indol-3-yl]carbonyl}-4-quinolinecarboxylate | C22H18N2O4 | 详情 | 详情 | |
| (VII) | 46800 | 12-(methoxymethyl)-7H-indolo[3,2-j]phenanthridine-7,13(12H)-dione | C21H14N2O3 | 详情 | 详情 |