2251-65-2Relevant articles and documents
Inhibitors of ribosome rescue arrest growth of francisella tularensis at all stages of intracellular replication
Goralski, Tyler D. P.,Dewan, Kalyan K.,Alumasa, John N.,Avanzato, Victoria,Place, David E.,Markley, Rachel L.,Katkere, Bhuvana,Rabadi, Seham M.,Bakshi, Chandra Shekhar,Keiler, Kenneth C.,Kirimanjeswara, Girish S.
, p. 3276 - 3282 (2016)
Bacteria require at least one pathway to rescue ribosomes stalled at the ends of mRNAs. The primary pathway for ribosome rescue is trans-translation, which is conserved in >99% of sequenced bacterial genomes. Some species also have backup systems, such as ArfA or ArfB, which can rescue ribosomes in the absence of sufficient trans-translation activity. Small-molecule inhibitors of ribosome rescue have broad-spectrum antimicrobial activity against bacteria grown in liquid culture. These compounds were tested against the tier 1 select agent Francisella tularensis to determine if they can limit bacterial proliferation during infection of eukaryotic cells. The inhibitors KKL-10 and KKL-40 exhibited exceptional antimicrobial activity against both attenuated and fully virulent strains of F. tularensis in vitro and during ex vivo infection. Addition of KKL-10 or KKL-40 to macrophages or liver cells at any time after infection by F. tularensis prevented further bacterial proliferation. When macrophages were stimulated with the proinflammatory cytokine gamma interferon before being infected by F. tularensis, addition of KKL-10 or KKL-40 reduced intracellular bacteria by >99%, indicating that the combination of cytokine-induced stress and a nonfunctional ribosome rescue pathway is fatal to F. tularensis. Neither KKL-10 nor KKL-40 was cytotoxic to eukaryotic cells in culture. These results demonstrate that ribosome rescue is required for F. tularensis growth at all stages of its infection cycle and suggest that KKL-10 and KKL-40 are good lead compounds for antibiotic development.
Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
supporting information, p. 5022 - 5037 (2021/05/04)
Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
Ni-Catalyzed C(sp2)-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as structurally diverse alkyl sources
Kano, Taichi,Maruoka, Keiji,Matsumoto, Akira,Sakurai, Shunya,Tsuzuki, Saori
supporting information, p. 7942 - 7945 (2021/08/17)
A Ni-catalyzed direct C-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as alkyl-radical precursors is described. The reaction forms a new C(sp3)-C(sp2) bondviathe selective cleavage of both C(sp3)-C(sp3) and C(sp2)-H bonds. This transformation shows a high functional-group tolerance and, due to the structural diversity of alkylsilyl peroxides, a wide range of alkyl chains including functional groups and complex structures can be introduced at theortho-position of readily availableN-quinolylbenzamide derivatives. Mechanistic studies suggest that the reaction involves a radical mechanism.
Copper-mediated C–H thiolation of (hetero)arenes using weakly coordinating directing group
Wu, Peng,Cheng, Tai-Jin,Lin, Hai-Xia,Xu, Hui,Dai, Hui-Xiong
supporting information, (2020/06/17)
We have developed a copper-mediated C–H thiolation of (hetero)arenes by using monodentate amide as weakly coordinating directing group. This protocol features excellent functional group tolerance and shows satisfactory compatibility with various heterocycles, such as indole, pyrrole, imidazole, pyridine, thiophene and quinoline. The robust nature of this protocol renders that it has potential value in the synthetic application.
