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A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation

文献类型：期刊论文

作者Chen, Lu2,3; Quan, Haitian2,3; Xu, Zhongliang2,3; Wang, Hao2,3; Xia, Yuanzhi1; Lou, Liguang2,3; Yang, Weibo2,3,4
刊名NATURE COMMUNICATIONS
出版日期2020-05-01
卷号11期号:1页码:8
ISSN号2041-1723
DOI10.1038/s41467-020-16084-0
通讯作者Lou, Liguang(lglou@simm.ac.cn) ; Yang, Weibo(yweibo@simm.ac.cn)
英文摘要One of the key challenges to overcome multidrug resistance (MDR) in cancer is the development of more effective and general strategies to discover bioactive scaffolds. Inspired by natural products, we describe a strategy to achieve this goal by modular biomimetic synthesis of scaffolds of (Z)-allylic-supported macrolides. Herein, an Rh(III)-catalyzed native carboxylic acid-directed and solvent-free C-H activation allylation with high stereoselectivity and chemoselectivity is achieved. The generated poly-substituted allylic alcohol as a multifunctional and biomimetic building block is crucial for the synthesis of (Z)-allylic-supported macrolides. Moreover, the unique allylic-supported macrolides significantly potentiate the sensitivity of tumor cells to cytotoxic agents such as vinorelbine and doxetaxel by reversing p170-glycoprotein-mediated MDR. Our findings will inspire the evolution of synthetic chemistry and open avenues for expedient and diversified synthesis of bioactive macrocyclic molecules. One strategy to address multidrug resistance in cancer is the development of modular methods to access bioactive scaffolds. Here, the authors report a Rh(III)-catalyzed carboxylic acid-directed C(sp(2))-H allylation and apply it to the modular synthesis of (Z)-allylic macrolides which enhance antitumoral drug activity.
WOS关键词BOND FUNCTIONALIZATIONS ; ALLYLATION ; MACROCYCLES
资助项目100 talent program of Chinese Academy of Sciences, NSFC[21702217] ; 1000-Youth Talents Plan, Shanghai-Youth Talent, National Science & Technology Major Project Key New Drug Creation and Manufacturing Program China[2018ZX09711002-006] ; Shanghai-Technology Innovation Action Plan[18JC1415300] ; Science and Technology Commission of Shanghai Municipality[18DZ2293200]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000531425700032
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/291681]  
专题中国科学院上海药物研究所
通讯作者Lou, Liguang; Yang, Weibo
作者单位1.Wenzhou Univ, Coll Chem & Mat Engn, Wenzhou 325035, Peoples R China
2.Chinese Acad Sci, Chinese Acad Sci Key Lab Receptor Res, Shanghai Inst Mat Med SIMM, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Sci & Technol Liaoning, Key Lab Funct Mat, Educ Dept Liaoning Prov, Anshan 114051, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Lu,Quan, Haitian,Xu, Zhongliang,et al. A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation[J]. NATURE COMMUNICATIONS,2020,11(1):8.
APA Chen, Lu.,Quan, Haitian.,Xu, Zhongliang.,Wang, Hao.,Xia, Yuanzhi.,...&Yang, Weibo.(2020).A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation.NATURE COMMUNICATIONS,11(1),8.
MLA Chen, Lu,et al."A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation".NATURE COMMUNICATIONS 11.1(2020):8.

入库方式： OAI收割

来源：上海药物研究所

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