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【结 构 式】 
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【分子编号】49945 【品名】(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 【CA登记号】 |
【 分 子 式 】C35H30N2O8S 【 分 子 量 】638.69788 【元素组成】C 65.82% H 4.73% N 4.39% O 20.04% S 5.02% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Treatment of (XIII) with aqueous trifluoroacetic acid produced simultaneous ketal group hydrolysis and lactonization, yielding intermediate (XIV). Optionally, basic hydrolysis of the ester groups of (XIII) with LiOH produced the lithium carboxylate salt (XV). Lactonization of (XV) with HOAc in chloroform gave (XVI). The cyclic ketal group of (XVI) was then hydrolyzed with aqueous trifluoroacetic acid to produce the intermediate (XVII). Alternatively, (XVII) was also produced by simultaneous hydrolysis and cyclization of (XV) with aqueous trifluoroacetic acid or by basic hydrolysis of (XIV), followed by acidic treatment. Intermediate (XIX) was prepared by acetylation of (XVI) followed by acidic hydrolysis of the resulting ketal (XVIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XIII) | 49943 | C44H48N2O11S | 详情 | 详情 | ||
| (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 | |
| (XV) | 49946 | C18H24LiNO7 | 详情 | 详情 | ||
| (XVI) | 49947 | C18H23NO6 | 详情 | 详情 | ||
| (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 | |
| (XVIII) | 49948 | C20H25NO7 | 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 |
合成路线2
该中间体在本合成路线中的序号：(XIV)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 |