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【结 构 式】

【分子编号】62245

【品名】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

【CA登记号】

【 分 子 式 】C35H33N3O13

【 分 子 量 】703.65944

【元素组成】C 59.74% H 4.73% N 5.97% O 29.56%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XV)

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
Extended Information