Total Synthesis of 7-Ethyl-10-hydroxycamptothecin (SN38) and its Application to the Development of C18-Functionalized Camptothecin Derivatives
文献类型：期刊论文
| 作者 | Yao, Yuan-Shan2,3; Liu, Jia-Li1; Xi, Jie2; Miu, Bukeyan2; Liu, Guai-Sai2; Wang, Shaozhong2; Meng, Linghua1 ; Yao, Zhu-Jun2
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| 刊名 | CHEMISTRY-A EUROPEAN JOURNAL
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| 出版日期 | 2011-09 |
| 卷号 | 17期号:37页码:10462-10469 |
| 关键词 | antitumor agents camptothecin derivatives Diels-Alder reaction structure-activity relationships total synthesis |
| ISSN号 | 0947-6539 |
| DOI | 10.1002/chem.201101389 |
| 文献子类 | Article |
| 英文摘要 | A new chemical synthesis of SN38, the active metabolite of the camptothecin prodrug irinotecan, has been achieved in 12 steps from simple, commercially available starting materials. A mild and efficient FeCl3-catalyzed Friedlander condensation was successfully applied to construct the AB ring system. Functionalization of the C ring was accomplished by a vinylogous Mukaiyama reaction of an in situ generated N-acyliminium intermediate with a silyl enol ether. An intramolecular oxa Diels-Alder reaction efficiently constructed the D and E rings in one step. Successive asymmetric dihydroxylation and I-2-based hemiacetal oxidation furnished the stereo-chemistry of SN38 with high enantiopurity. Utilizing the ABC-ring intermediate and a functionalized silyl enol ether permitted the synthesis of a number of new C18-functionalized SN38 derivatives. Several of the novel SN38 derivatives that bore a C10 methoxy group were found to exhibit comparable or more potent inhibitory activity against the proliferation of cancer cells relative to SN38. |
| WOS关键词 | DNA TOPOISOMERASE-I ; CATALYTIC ASYMMETRIC DIHYDROXYLATION ; PLANT ANTITUMOR AGENTS ; VITRO CYTOTOXICITY ; ANALOGS ; STRATEGY ; RING ; EFFICIENT ; CANCER ; (20S)-CAMPTOTHECIN |
| 资助项目 | NSFC[21032002] ; Ministry of Health[2009ZX09501] ; 973 Program[2010CB833200] ; Fundamental Research Funds for the Central Universities[1082020502] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000295457700032 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278413]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Meng, Linghua |
| 作者单位 | 1.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Nanjing Univ, State Key Lab Coordinat Chem, Nanjing Natl Lab Microstruct, Inst Chem Biol & Drug Innovat,Sch Chem & Chem Eng, Nanjing 210093, Jiangsu, Peoples R China; 3.Univ Sci & Technol China, Joint Lab Green Chem, Dept Chem, Hefei 230026, Anhui, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yao, Yuan-Shan,Liu, Jia-Li,Xi, Jie,et al. Total Synthesis of 7-Ethyl-10-hydroxycamptothecin (SN38) and its Application to the Development of C18-Functionalized Camptothecin Derivatives[J]. CHEMISTRY-A EUROPEAN JOURNAL,2011,17(37):10462-10469. |
| APA | Yao, Yuan-Shan.,Liu, Jia-Li.,Xi, Jie.,Miu, Bukeyan.,Liu, Guai-Sai.,...&Yao, Zhu-Jun.(2011).Total Synthesis of 7-Ethyl-10-hydroxycamptothecin (SN38) and its Application to the Development of C18-Functionalized Camptothecin Derivatives.CHEMISTRY-A EUROPEAN JOURNAL,17(37),10462-10469. |
| MLA | Yao, Yuan-Shan,et al."Total Synthesis of 7-Ethyl-10-hydroxycamptothecin (SN38) and its Application to the Development of C18-Functionalized Camptothecin Derivatives".CHEMISTRY-A EUROPEAN JOURNAL 17.37(2011):10462-10469. |
入库方式： OAI收割
来源：上海药物研究所
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