Diversified strategy for the synthesis of DNA-encoded oxindole libraries.
Xuan Wang,Jiaxiang Liu,Ziqin Yan,Xiaohong Liu,Xiaohong Liu,Sixiu Liu,Yanrui Suo,Weiwei Lu,Jinfeng Yue,Kaixian Chen,Kaixian Chen,Hualiang Jiang,Hualiang Jiang,Yujun Zhao,Mingyue Zheng,Dongcheng Dai,Xiaojie Lu +16 more
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TLDR
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 are reported.Abstract:
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.read more
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High-power screening (HPS) empowered by DNA-encoded libraries
TL;DR: High-power screening (HPS) as discussed by the authors has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.
Journal ArticleDOI
High-power screening (HPS) empowered by DNA-encoded libraries
TL;DR: High-power screening (HPS) as mentioned in this paper has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.
Journal ArticleDOI
Highly efficient on-DNA amide couplings promoted by micelle forming surfactants for the synthesis of DNA encoded libraries.
James H. Hunter,Matthew J. Anderson,Isaline F.S.F. Castan,Jessica S. Graham,Catherine L.A. Salvini,Harriet A. Stanway-Gordon,Crawford James John,Andrew Madin,Garry Pairaudeau,Michael J. Waring +9 more
TL;DR: In this article, a method for amide coupling using micelle forming surfactants, promoted by a modified linker, was proposed for coupling DNA-conjugated carboxylic acids with amines in solution, a procedure that is currently very inefficient.
Journal ArticleDOI
Functionalization of DNA-Tagged Alkenes Enabled by Visible-Light-Induced C–H Activation of N-Aryl Tertiary Amines
TL;DR: In this paper, a highly efficient approach to C(sp3)-C(sp 3) bond construction via photoredox catalysis between on-DNA alkenes and N-aryl tertiary amines was developed.
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