Diversified strategy for the synthesis of DNA-encoded oxindole libraries

doi:10.1039/d0sc06696f

	Diversified strategy for the synthesis of DNA-encoded oxindole libraries
	Wang, Xuan 3,4; Liu, Jiaxiang 3; Yan, Ziqin 3; Liu, Xiaohong 1,2,5; Liu, Sixiu 3; Suo, Yanrui 3; Lu, Weiwei 3; Yue, Jinfeng 3; Chen, Kaixian 1,2,5; Jiang, Hualiang 1,2,5
刊名	CHEMICAL SCIENCE
	2021-02-28
卷号	12 期号:8 页码:2841-2847
ISSN号	2041-6520
DOI	10.1039/d0sc06696f
通讯作者	Zhao, Yujun() ; Zheng, Mingyue() ; Dai, Dongcheng() ; Lu, Xiaojie(xjlu@simm.ac.cn)
英文摘要	DNA-encoded library technology (DELT) employs DNA as a barcode to track the sequence of chemical reactions and enables the design and synthesis of libraries with billions of small molecules through combinatorial expansion. This powerful technology platform has been successfully demonstrated for hit identification and target validation for many types of diseases. As a highly integrated technology platform, DEL is capable of accelerating the translation of synthetic chemistry by using on-DNA compatible reactions or off-DNA scaffold synthesis. Herein, we report the development of a series of novel on-DNA transformations based on oxindole scaffolds for the design and synthesis of diversity-oriented DNA-encoded libraries for screening. Specifically, we have developed 1,3-dipolar cyclizations, cyclopropanations, ring-opening of reactions of aziridines and Claisen-Schmidt condensations to construct diverse oxindole derivatives. The majority of these transformations enable a diversity-oriented synthesis of DNA-encoded oxindole libraries which have been used in the successful hit identification for three protein targets. We have demonstrated that a diversified strategy for DEL synthesis could accelerate the application of synthetic chemistry for drug discovery.
资助项目	National Natural Science Foundation of China[81773634] ; National Natural Science Foundation of China[21877117] ; National Natural Science Foundation of China[91953203] ; National Natural Science Foundation of China[21907103] ; National Natural Science Foundation of China[81673295] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-005] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040330] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050405] ; Shanghai Commission of Science and Technology[18431907100]
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000625958900008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295360]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Yujun; Zheng, Mingyue; Dai, Dongcheng; Lu, Xiaojie
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd,Zhang Jiang Hitech Pk, Shanghai 201203, Peoples R China 4.Amgen Biopharmaceut R&D Shanghai Co Ltd, Amgen Asia R&D Ctr, 4560 Jinke Rd,Bldg 2,13th Floor, Shanghai 201210, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xuan,Liu, Jiaxiang,Yan, Ziqin,et al. Diversified strategy for the synthesis of DNA-encoded oxindole libraries[J]. CHEMICAL SCIENCE,2021,12(8):2841-2847.
APA	Wang, Xuan.,Liu, Jiaxiang.,Yan, Ziqin.,Liu, Xiaohong.,Liu, Sixiu.,...&Lu, Xiaojie.(2021).Diversified strategy for the synthesis of DNA-encoded oxindole libraries.CHEMICAL SCIENCE,12(8),2841-2847.
MLA	Wang, Xuan,et al."Diversified strategy for the synthesis of DNA-encoded oxindole libraries".CHEMICAL SCIENCE 12.8(2021):2841-2847.