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【结 构 式】 
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【分子编号】49955 【品名】tert-butyl 3-[[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy]propylcarbamate 【CA登记号】 |
【 分 子 式 】C30H35N3O7 【 分 子 量 】549.62392 【元素组成】C 65.56% H 6.42% N 7.65% O 20.38% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)The title compound was prepared from aminopropiophenone (XXVII) by several procedures. Aldol condensation of (XXVII) with the intermediate pyranoindolizinetrione (XVII) with concomitant Friedlander quinoline synthesis under acidic conditions furnished the camptothecin derivative (XXVIII). Optionally, (XXVIII) was also obtained by condensation of (XXVII) with intermediate ketone (XIX), followed by basic hydrolysis of the resultant lactone-ester (XXIX) and subsequent relactonization under acidic conditions. Finally, acid cleavage of the N-Boc group of (XXVII) yielded the title compound.
| 【1】 Tsujihara, K.; Kawaguchi, T.; Okuno, S.; Yano, T. (Tanabe Seiyaku Co., Ltd.); Camptothecin derivs.. CA 2182244; EP 0757049; JP 1998072467; US 5837673 . |
| 【2】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 10841 | (4S)-4-Ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione | C13H13NO5 | 详情 | 详情 | |
| (XIX) | 49949 | (4S)-4-ethyl-3,6,10-trioxo-3,4,6,7,8,10-hexahydro-1H-pyrano[3,4-f]indolizin-4-yl acetate | C15H15NO6 | 详情 | 详情 | |
| (XXVII) | 49954 | tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate | C17H26N2O4 | 详情 | 详情 | |
| (XXVIII) | 49955 | tert-butyl 3-[[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy]propylcarbamate | C30H35N3O7 | 详情 | 详情 | |
| (XXIX) | 49956 | (4S)-9-[3-[(tert-butoxycarbonyl)amino]propoxy]-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl acetate | C32H37N3O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXVIII)In an alternative procedure, condensation of aminopropiophenone (XXVII) with the intermediate pyranoindolizinetrione (XIV) under acidic conditions gave rise to camptothecin derivative (XXX). Basic hydrolysis of the chiral auxiliary ester and lactone groups of (XXX) followed by acidic relactonization then gave the precursor (XXVIII), which was finally subjected to Boc group cleavage as indicated above.
| 【1】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 49945 | (4S)-4-ethyl-3,6,10-trioxo-3,4,6,7,8,10-hexahydro-1H-pyrano[3,4-f]indolizin-4-yl (3R)-2-([1,1'-biphenyl]-4-ylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C35H30N2O8S | 详情 | 详情 | |
| (XXVII) | 49954 | tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate | C17H26N2O4 | 详情 | 详情 | |
| (XXVIII) | 49955 | tert-butyl 3-[[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy]propylcarbamate | C30H35N3O7 | 详情 | 详情 | |
| (XXX) | 49957 | (4S)-9-[3-[(tert-butoxycarbonyl)amino]propoxy]-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl (3R)-2-([1,1'-biphenyl]-4-ylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C52H52N4O10S | 详情 | 详情 |