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【结 构 式】 
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【分子编号】62243 【品名】(4S)-4-ethyl-4-hydroxy-10-isocyanato-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione 【CA登记号】 |
【 分 子 式 】C21H15N3O5 【 分 子 量 】389.36732 【元素组成】C 64.78% H 3.88% N 10.79% O 20.55% |
合成路线1
该中间体在本合成路线中的序号：(XIII)10-Hydroxycamptothecin (IX) is nitrated with HNO3/H2SO4 and the resulting 9-nitro-10-hydroxycamptothecin (X) is treated with tosyl chloride to form the tosylate (XI). Palladium-catalyzed reduction of nitro tosylate (XI) gives rise to 9-aminocapmtothecin (XII). Amine (XII) is activated as the isocyanate (XIII) upon treatment with triphosgene (1) or alternatively as the aryl carbamate (XIV) employing p-nitrophenyl chloroformate. Coupling of either isocyanate (XIII) or carbamate (XIV) with p-hydroxybenzyl alcohol glucuronide (VIII) leads to adduct (XV). The methyl glucuronate ester (XV) is finally hydrolyzed to the target acid under anhydrous conditions by using potassium trimethylsilanolate.
| 【1】 Leu, Y.-L.; Roffler, S.R.; Chern, J.-W.; Design and synthesis of water-soluble glucuronide derivatives of camptothecin for cancer prodrug monotherapy and antibody-directed enzyme prodrug therapy (ADEPT). J Med Chem 1999, 42, 18, 3623. |
| 【2】 Chern, J.-W.; Roffler, S.; Leu, Y.-L. (Academia Sinica); Proactive antitumor cpds.. EP 0990661; US 6043367 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 62241 | methyl (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[4-(hydroxymethyl)phenoxy]tetrahydro-2H-pyran-2-carboxylate | C14H18O8 | 详情 | 详情 | |
| (IX) | 13340 | (4S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxycamptothecin | 86639-52-3 | C20H16N2O5 | 详情 | 详情 |
| (X) | 43901 | (4S)-4-ethyl-4,9-dihydroxy-10-nitro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C20H15N3O7 | 详情 | 详情 | |
| (XI) | 43902 | (4S)-4-ethyl-4-hydroxy-10-nitro-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl 4-methylbenzenesulfonate | C27H21N3O9S | 详情 | 详情 | |
| (XII) | 44148 | (4S)-10-amino-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C20H17N3O4 | 详情 | 详情 | |
| (XIII) | 62243 | (4S)-4-ethyl-4-hydroxy-10-isocyanato-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | C21H15N3O5 | 详情 | 详情 | |
| (XIV) | 62244 | 4-nitrophenyl (4S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-10-ylcarbamate | C27H20N4O8 | 详情 | 详情 | |
| (XV) | 62245 | methyl (2S,3S,4S,5R)-6-(4-{[({[(4S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-10-yl]amino}carbonyl)oxy]methyl}phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate | C35H33N3O13 | 详情 | 详情 |