An overview of reductive trifluoromethylation reactions using electrophilic ‘+CF3’ reagents

Wang, Shi‐Meng; Han, Jiahuai; Zhang, Cheng‐Pan; Qin, Hua‐Li; Xiao, Ji‐Chang

doi:10.1016/j.tet.2015.06.056

Cited by 106 publications

(29 citation statements)

References 124 publications

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“…CTNNA2 (Catenin Alpha 2) encodes a protein involved in cell-cell adhesion (Janssens et al, 2001), found to play a role in synapse morphogenesis and plasticity (Arikkath and Reichardt, 2008;Arikkath et al, 2009). CEP120 (Centrosomal Protein 120) encodes Cep120, vital for Interkinetic Nuclear Migration (INM) in neural progenitor cells of the cortex (Guerrier and Polleux, 2007).…”

Section: Genes Of Interest Identified In Gwas Of Mcpmentioning

confidence: 99%

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Johnston

Adams

Nicholl

et al. 2018

Preprint

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Chronic pain is highly prevalent worldwide, contributing a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype, chronic pain grade, have been shown to be complex, heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested. We have here made use of a measure of the number of sites of chronic pain in individuals within the general UK population. This measure, termed Multisite Chronic Pain (MCP), is also a complex trait, but its genetic architecture has not previously been investigated. To address this, a large-scale genome-wide association study (GWAS) of MCP was carried out in ~380,000 UK Biobank participants to identify associated genetic variants. Findings were consistent with MCP having a significant polygenic component with a SNP heritability of 10.2%, and 76 independent lead single nucleotide polymorphisms (SNPs) at 39 risk loci were identified. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as being enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits including major depressive disorder (MDD), asthma and BMI. Furthermore, in Mendelian randomisation (MR) analyses a bi-directional causal relationship was observed between MCP and MDD. A polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. These findings support the proposition that chronic pain involves a strong nervous system component and have implications for our understanding of the physiology of chronic pain and for the development of novel treatment strategies.

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Section: Genes Of Interest Identified In Gwas Of Mcpmentioning

confidence: 99%

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Johnston

Adams

Nicholl

et al. 2018

Preprint

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“…Introduction of aC F 3 group into organic molecules can substantially affect biological properties including lipophilicity,bioavailability,and capacity to penetrate the blood-brain barrier, making it ap otent tool in agricultural and medicinal chemistry. [1][2][3][4][5][6][7] Numerous,v aried methods for the preparation of CF 3 -containing molecules have been developed. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Efforts to avoid prefunctionalized or electronically activated starting materials have focused attention on direct functionalization of unactivated C À Hbonds, [8,19,23] spurring a"renaissance" in radical trifluoromethylations.…”

mentioning

confidence: 99%

Photoinduced Cobalt(III)−Trifluoromethyl Bond Activation Enables Arene C−H Trifluoromethylation

et al. 2018

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Visible-light capture activates a thermodynamically inert Co -CF bond for direct C-H trifluoromethylation of arenes and heteroarenes. New trifluoromethylcobalt(III) complexes supported by a redox-active [OCO] pincer ligand were prepared. Coordinating solvents, such as MeCN, afford green, quasi-octahedral [( OCO)Co (CF )(MeCN) ] (2), but in non-coordinating solvents the complex is red, square pyramidal [( OCO)Co (CF )(MeCN)] (3). Both are thermally stable, and 2 is stable in light. But exposure of 3 to low-energy light results in facile homolysis of the Co -CF bond, releasing CF radical, which is efficiently trapped by TEMPO or (hetero)arenes. The homolytic aromatic substitution reactions do not require a sacrificial or substrate-derived oxidant because the Co by-product of Co -CF homolysis produces H . The photophysical properties of 2 and 3 provide a rationale for the disparate light stability.

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“…Trifluoromethylated cyclic λ 3 ‐iodanes (Togni reagents) and their tetrafluoroethylene‐containing analogues 1 have been previously used as electrophilic fluoroalkylating species in reactions with various sulfur‐, oxygen‐, phosphorus‐, and carbon‐centered nucleophiles and also thiol containing biomolecules including bioconjugations of Cys residues (Figure A) . The concept of reductive trifluoromethylation of small molecules, such as alkenes or aromatics by using Togni reagents and transition‐metal (Cu, Fe and the photochemical use of Ru or Ir) or non‐metallic [NaI, TEMPONa (TEMPO=2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl)] reductants has been realized successfully on several examples (Figure B) . However, the reported conditions did not allow to perform this functionalization with biomolecules in aqueous environment under ambient conditions.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] The concept of reductive trifluoromethylation of small molecules, such as alkenes or aromatics by usingT ogni reagentsa nd transition-metal (Cu, Fe and the photochemical use of Ru or Ir) or non-metallic [NaI, TEMPONa (TEMPO = 2,2,6,6-tetramethylpiperidin-1-yl)oxyl)] reductants has been realizeds uccessfully on several examples ( Figure 1B). [13,14] However,t he reported conditionsd id not allow to perform thisf unctionalization with biomolecules in aqueous environment under ambient conditions. Here, we describe the development of ar adical functionalization methodb ased on the reduction of l 3 -iodanes with watersoluble andbiocompatiblereductant targetings mall molecules (indoles,p yrroles) and peptides or proteinso na romatic amino acid residues with high selectivity to tryptophan (Figure1C).…”

Section: Introductionmentioning

confidence: 99%

Reductant‐Induced Free Radical Fluoroalkylation of Nitrogen Heterocycles and Innate Aromatic Amino Acid Residues in Peptides and Proteins

Rahimidashaghoul

Klimánková

Hubálek

et al. 2019

Chemistry A European J

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A series of fluoroalkylated cyclic λ3‐iodanes and their hydrochloride salts was prepared and used in a combination with sodium ascorbate in buffer or aqueous methanol mixtures for radical fluoroalkylation of a range of substituted indoles, pyrroles, tryptophan or its derivatives, and Trp residues in peptides. As demonstrated on several peptides, the aromatic amino acid residues of Trp, Tyr, Phe, and His are targeted with high selectivity to Trp. The functionalization method is biocompatible, mild, rapid, and transition‐metal‐free. The proteins myoglobin, ubiquitin, and human carbonic anhydrase I were also successfully functionalized.

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An overview of reductive trifluoromethylation reactions using electrophilic ‘+CF3’ reagents

Cited by 106 publications

References 124 publications

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Photoinduced Cobalt(III)−Trifluoromethyl Bond Activation Enables Arene C−H Trifluoromethylation

Reductant‐Induced Free Radical Fluoroalkylation of Nitrogen Heterocycles and Innate Aromatic Amino Acid Residues in Peptides and Proteins

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