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# Organic Chemistry #

Monofluoromethyl-Substituted Sulfonium Ylides: Electrophilic Monofluoromethylating Reagents with Broad Substrate Scopes

Angew. Chem. Int. Ed.

First published: 10 July 2017

DOI: 10.1002/anie.201704175

Yafei Liu, Prof. Dr. Long Lu and Prof. Dr. Qilong Shen

Abstract:Two electrophilic monofluoromethylating reagents, monofluoromethyl(phenyl)sulfonium bis(carbomethoxy)methylide (3 a) and monofluoromethyl(4-nitrophenyl)sulfonium bis(carbomethoxy)methylide (3 b), and their reactions under mild conditions with a variety of nucleophiles, such as alcohols and malonate derivatives, sulfonic and carboxylic acids, phenols, amides, and N heteroarenes, are described. Mechanistic studies with deuterated reagents [D₂]3 a/[D₂]3 b suggest that these monofluoromethylation reactions proceed through an electrophilic substitution pathway.

Link to CBG：

http://www.chembeango.com/news/art?id=4709

Link to the article：

http://onlinelibrary.wiley.com/doi/10.1002/anie.201704175/full

# Medicinal Chemistry #

Discovery of Potent and Selective Inhibitors of Cdc2-like Kinase 1 (CLK1) as a New Class of Autophagy Inducers

Journal of Medicinal Chemistry

Publication Date (Web): July 10, 2017

DOI: 10.1021/acs.jmedchem.7b00665

Qi-Zheng Sun, Gui-Feng Lin, Lin-Li Li, Xi-Ting Jin, Lu-Yi Huang, Guo Zhang, Wei Yang, Kai Chen, Rong Xiang, Chong Chen, Yu-Quan Wei, Guang-Wen Lu, and Sheng-Yong Yang

Abstract:Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound 25 was solved, and the potency and kinase selectivity of compound 25 were interpreted. Compound 25 was able to induce autophagy in in vitro assays and displayed significant hepatoprotective effects in the acetaminophen (APAP)-induced liver injury mouse model. Collectively, due to its potency and selectivity, compound 25 could be used as a chemical probe or agent in future mechanism-of-action or autophagy-related disease therapy studies.

Link to CBG：

http://www.chembeango.com/news/art?id=4745

Link to the article：

http://pubs.acs.org/doi/10.1021/acs.jmedchem.7b00665

# Biological Chemistry #

Tuning the Inter-nanofibril Interaction to Regulate the Morphology and Function of Peptide/DNA Co-assembled Viral Mimics

Angew. Chem. Int. Ed.

First published: 10 July 2017

DOI: 10.1002/anie.201703596

Dr. Rong Ni and Prof. Dr. Ying Chau

Abstract:The ability to tune the inter-subunit interaction within the virus capsid may be critical to assembly and biological function. This process was extended here with peptide/DNA co-assembled viral mimics. The resulting co-assemblies, formed and stabilized by both peptide nanofibril–DNA and peptide nanofibril–nanofibril interactions, were tuned through hydrophobic packing interactions of the peptide sequences. By strengthening peptide side-chain complementarity and/or elongating the peptide chain (from 4 to 8 residues), we report strengthening the inter-nanofibril interaction to create stable nanococoons that give high gene-transfection efficacy.

Link to CBG：

http://www.chembeango.com/news/art?id=4715

Link to the article：

http://onlinelibrary.wiley.com/doi/10.1002/anie.201703596/full

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