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Browsing by Author "Yang, Ke"
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Item 14-3-3σ Contributes to Radioresistance by Regulating DNA Repair and Cell Cycle via PARP1 and CHK2(AACR, 2017) Chen, Yifan; Li, Zhaomin; Dong, Zizheng; Beebe, Jenny; Yang, Ke; Fu, Liwu; Zhang, Jian-Ting; Department of Pharmacology and Toxicology, IU School of Medicine14-3-3σ has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3σ contributes to these resistances via inhibiting apoptosis and arresting cells in G2–M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3σ causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2–M phase following DNA-damaging treatments. We showed that 14-3-3σ contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2–M phase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSB). The increased NHEJ repair activity was due to 14-3-3σ–mediated upregulation of PARP1 expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2–M arrest following IR was due to 14-3-3σ–induced Chk2 expression. Implications: These findings reveal an important molecular basis of 14-3-3σ function in cancer cell resistance to chemo/radiation therapy and in poor prognosis of human cancers.Item Benzisothiazol‐3‐ones through a Metal‐Free Intramolecular N–S Bond Formation(Wiley, 2018-11) Yang, Ke; Zhang, Hao; Niu, Ben; Tang, Tiandi; Ge, Haibo; Chemistry and Chemical Biology, School of ScienceThe highly efficient synthesis of benzoisothiazol‐3‐ones from thiobenzamides has been described with good functional group compatibility and excellent yields. This work represents the first example of selectfluor‐promoted N–S bond formation processes. This method provides a facile approach to access various important bioactive benzoisothiazol‐3‐ones.Item Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons(Nature Publishing Group, 2015-03-10) Wu, Xuesong; Yang, Ke; Zhao, Yan; Sun, Hao; Li, Guigen; Ge, Haibo; Department of Chemistry & Chemical Biology, School of ScienceCobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized., Functionalizing unactivated carbon–hydrogen bonds is challenging, especially when using non-precious metals and dealing with sp3 hybridized carbons. Here, the authors report an intramolecular cobalt catalysed amination of C–H bonds of sp3 carbons, giving access to β- and γ-lactams.Item Palladium-catalyzed ligand-promoted site-selective cyanomethylation of unactivated C(sp3)–H bonds with acetonitrile(RSC, 2016-04-21) Liu, Yongbing; Yang, Ke; Ge, Haibo; Department of Chemistry & Chemical Biology, School of ScienceThe direct cyanomethylation of unactivated sp3 C–H bonds of aliphatic amides was achieved via palladium catalysis assisted by a bidentate directing group with good functional group compatibility. This process represents the first example of the direct cross-coupling of sp3 C–H bonds with acetonitrile. Considering the importance of the cyano group in medicinal and synthetic organic chemistry, this reaction will find broad application in chemical research.Item Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp3)−H Bonds(ACS, 2015-07) Miao, Jinmin; Yang, Ke; Kurek, Martin; Ge, Haibo; Department of Chemistry & Chemical Biology, School of ScienceThe transition-metal-catalyzed direct C–H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp3 C–H functionalization, site-selective fluorination of unactivated sp3 carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C–H bond functionalization process on unactivated sp3 carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source.Item Silver-Promoted Site-Selective Intramolecular Cyclization of 2-Methylthiobenzamide Through α-C(sp3)–H Functionalization(ACS, 2019-11) Yang, Ke; Niu, Ben; Ma, Zhiyan; Wang, Hui; Lawrence, Brianna; Ge, Haibo; Chemistry and Chemical Biology, School of ScienceSilver-mediated intramolecular α-C(sp3)–H bond functionalization of the methylthio group has been established in the presence of Selectfluor as an additive. This novel strategy provides efficient access to various diverse sulfur-based heterocycles with good yields and functional group compatibility. It is noteworthy that the completely novel benzooxathiin-4-imine skeletons were reported for the first time in this study.Item Transient ligand‐enabled transition metal‐catalysed C‐H functionalisation(Wiley, 2019) Niu, Ben; Yang, Ke; Lawrence, Brianna; Ge, Haibo; Chemistry and Chemical Biology, School of ScienceTransition metal‐catalysed C‐H bond functionalisation is one of the most efficient and powerful strategies in synthetic organic chemistry to derivatize otherwise inert sites of organic molecules for the construction of C‐C and C‐heteroatom bonds. However, additional steps are often required in order to install the directing groups to realize the positional functionalisation of the substrates. These tedious steps run counter to the step‐economical nature of the C‐H activation. In contrast, direct functionalisation of the substrate, utilizing the transient ligands, avoids the unnecessary steps for the prefunctionalisation of the substrates. In this mini review, we will provide a short journey for the major progress made in this field for the C‐H functionalisation on sp2 and sp3 carbon centres with different transient working modes, including the covalent, hydrogen, and ionic bonds.