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

doi:10.1038/s41467-020-16084-0

	A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation
	Chen, Lu 2,3; Quan, Haitian 2,3; Xu, Zhongliang 2,3; Wang, Hao 2,3; Xia, Yuanzhi 1; Lou, Liguang 2,3; Yang, Weibo 2,3,4
刊名	NATURE COMMUNICATIONS
	2020-05-01
卷号	11 期号:1 页码:8
ISSN号	2041-1723
DOI	10.1038/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.
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关键词	BOND FUNCTIONALIZATIONS ; ALLYLATION ; MACROCYCLES
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000531425700032
内容类型	期刊论文
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.