- Construction of an isoquinolinone framework from carboxylic-ester-directed umpolung ring opening of methylenecyclopropanes
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An interesting type of reaction involving functionalized methylenecyclopropanes (MCPs) has been revealed. Here, a nucleophilic attack of an anionic species onto a partially polarity-reversed MCP was realized by treating a neighbouring carboxylic ester tethered to the MCP and amine with KHMDS to realize an umpolung ring opening of the MCP. This work established an operationally convenient protocol for the rapid construction of isoquinolinone frameworks. This journal is
- Wei, Hao-Zhao,Wei, Yin,Shi, Min
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supporting information
p. 11201 - 11204
(2021/11/09)
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- Discovery of Antibacterials That Inhibit Bacterial RNA Polymerase Interactions with Sigma Factors
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Formation of a bacterial RNA polymerase (RNAP) holoenzyme by a catalytic core RNAP and a sigma (σ) initiation factor is essential for bacterial viability. As the primary binding site for the housekeeping σ factors, the RNAP clamp helix domain represents an attractive target for novel antimicrobial agent discovery. Previously, we designed a pharmacophore model based on the essential amino acids of the clamp helix, such as R278, R281, and I291 (Escherichia coli numbering), and identified hit compounds with antimicrobial activity that interfered with the core-σ interactions. In this work, we rationally designed and synthesized a class of triaryl derivatives of one hit compound and succeeded in drastically improving the antimicrobial activity against Streptococcus pneumoniae, with the minimum inhibitory concentration reduced from 256 to 1 μg/mL. Additional characterization of antimicrobial activity, inhibition of transcription, in vitro pharmacological properties, and cytotoxicity of the optimized compounds demonstrated their potential for further development.
- Ye, Jiqing,Chu, Adrian Jun,Harper, Rachel,Chan, Shu Ting,Shek, Tsun Lam,Zhang, Yufeng,Ip, Margaret,Sambir, Mariya,Artsimovitch, Irina,Zuo, Zhong,Yang, Xiao,Ma, Cong
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p. 7695 - 7720
(2020/07/21)
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- COMPOUNDS WITH ANTIMICROBIAL ACTIVITY
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Provided herein are compounds useful in the treatment of bacterial infections, pharmaceuticals comprising the same, and methods of use and preparation thereof.
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Paragraph 0245; 0248; 0249
(2020/01/24)
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- Palladium-Catalyzed Environmentally Benign Acylation
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Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp2 C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.
- Suchand, Basuli,Satyanarayana, Gedu
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p. 6409 - 6423
(2016/08/16)
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