Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Site-Selective Synthesis of N-Benzyl 2,4,6-Collidinium Salts by Electrooxidative C-H Functionalization.

ABSTRACT: N-alkylpyridinium salts are versatile pseudohalides for SET-mediated cross couplings. However, the common 2,4,6-triphenylpyridinium salt is plagued by poor atom economy and high cost of synthesis. Thus, there is a growing need for more practical scaffolds and innovative strategies for pyridinium salt formation. Herein, we report the synthesis of benzylic 2,4,6-collidinium salts via electrooxidative C-H functionalization. This method provides a complementary approach to tradtional strategies relying on substitution and condensation of prefunctionalized substrates.

SUBMITTER: Motsch BJ

PROVIDER: S-EPMC9434718 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Site-Selective Synthesis of N-Benzyl 2,4,6-Collidinium Salts by Electrooxidative C-H Functionalization.

Motsch Bill J BJ Wengryniuk Sarah E SE

Organic letters 20220808 32

<i>N-</i>alkylpyridinium salts are versatile pseudohalides for SET-mediated cross couplings. However, the common 2,4,6-triphenylpyridinium salt is plagued by poor atom economy and high cost of synthesis. Thus, there is a growing need for more practical scaffolds and innovative strategies for pyridinium salt formation. Herein, we report the synthesis of benzylic 2,4,6-collidinium salts via electrooxidative C-H functionalization. This method provides a complementary approach to tradtional strategi ...[more]

PMID: 35938890

Similar Datasets

Site-Selective Amide Functionalization by Catalytic Azoline Engrafting.

Project description:Direct peptide and protein activation is a challenging transformation because of the stabilizing effect of the amide group. While enzymes can be considered as prototypical systems that have evolved to achieve high selectivity and specificity, small-molecule catalysts that functionalize the amide group may accommodate a much larger selection of substrates but currently remain scarce. Here, by combining the desired features from both catalytic regimes we designed an artificial cyclodehydratase, a catalytic system for the site-selective modification of peptides and natural products by engrafting heterocycles into their scaffolds. The catalytic system features a molybdenum(VI) center that was decorated with a sterically congested tripod ligand. The optimized catalyst can introduce azolines into small molecules, natural products, and oligopeptides with high efficiency and minimal waste. We further demonstrate the utility of the new protocol in the direct functionalization of a single amide group in the presence of up to seven other chemically similar positions and in the direct conversion of these groups into amines and thioamides. This new mechanistic paradigm may address an unmet need for a general method for the selective and sustainable functionalization of peptides and natural products.

| S-EPMC10153596 | biostudies-literature

Site-Selective RNA Functionalization via DNA-Induced Structure.

Project description:Methods for RNA functionalization at specific sites are in high demand but remain a challenge, particularly for RNAs produced by transcription rather than by total synthesis. Recent studies have described acylimidazole reagents that react in high yields at 2'-OH groups stochastically at nonbase-paired regions, covering much of the RNA in scattered acyl esters. Localized reactions, if possible, could prove useful in many applications, providing functional handles at specific sites and sequences of the biopolymer. Here, we describe a DNA-directed strategy for in vitro functionalization of RNA at site-localized 2'-OH groups. The method, RNA Acylation at Induced Loops (RAIL), utilizes complementary helper DNA oligonucleotides that expose gaps or loops at selected positions while protecting the remainder in DNA-RNA duplexes. Reaction with an acylimidazole reagent is then carried out, providing high yields of 2'-OH conjugation at predetermined sites. Experiments reveal optimal helper oligodeoxynucleotide designs and conditions for the reaction, and tests of the approach are carried out to control localized ribozyme activities and to label RNAs with dual-color fluorescent dyes. The RAIL approach offers a simple and novel strategy for site-selective labeling and control of RNAs, potentially of any length and origin.

| S-EPMC7962339 | biostudies-literature

Aryl Sulfonium Salts for Site-Selective Late-Stage Trifluoromethylation.

Project description:Incorporation of the CF3 group into arenes has found increasing importance in drug discovery. Herein, we report the first photoredox-catalyzed cross-coupling of aryl thianthrenium salts with a copper-based trifluoromethyl reagent, which enables a site-selective late-stage trifluoromethylation of arenes. The reaction proceeds with broad functional group tolerance, even for complex small molecules on gram scale. The method was further extended to produce pentafluoroethylated derivatives.

| S-EPMC7754511 | biostudies-literature

Site-Selective C-H Oxygenation via Aryl Sulfonium Salts.

Project description:Herein, we report a two-step process forming arene C-O bonds in excellent site-selectivity at a late-stage. The C-O bond formation is achieved by selective introduction of a thianthrenium group, which is then converted into C-O bonds using photoredox chemistry. Electron-rich, -poor and -neutral arenes as well as complex drug-like small molecules are successfully transformed into both phenols and various ethers. The sequence differs conceptually from all previous arene oxygenation reactions in that oxygen functionality can be incorporated into complex small molecules at a late stage site-selectively, which has not been shown via aryl halides.

| S-EPMC7754133 | biostudies-literature

Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate.

Project description:Rhodium-catalyzed C-H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C-H functionalization of N-Boc-piperidine using Rh2 (R-TCPTAD)4 , or N-brosyl-piperidine using Rh2 (R-TPPTTL)4 generated 2-substitited analogues. In contrast, when N-α-oxoarylacetyl-piperidines were used in combination with Rh2 (S-2-Cl-5-BrTPCP)4 , the C-H functionalization produced 4-susbstiuted analogues. Finally, the 3-substituted analogues were prepared indirectly by cyclopropanation of N-Boc-tetrahydropyridine followed by reductive regio- and stereoselective ring-opening of the cyclopropanes.

| S-EPMC7187323 | biostudies-literature

Wavelength-Selective Reactivity of Iron(III) Halide Salts in Photocatalytic C-H Functionalization.

Project description:The utility of halogen radicals in hydrocarbon functionalization extends from early examples of photochemical halogenation to recent reports using photoredox catalysis with iridium complexes and simple transition metal salts such as FeCl3. The majority of these methods (uncatalyzed and iron-catalyzed) require UV light (λ ≤ 390 nm), and systematic efforts to enable the use of visible light remain valuable. We report the use of a simple Fe(III) salt that enables a C-H to C-C and C-N functionalization under visible light. The reactivity and selectivity profile using different light sources demonstrates wavelength-selective behavior, which was further investigated with deuterium kinetic isotope effect experiments and DFT calculations. These results show that control over the reactive intermediates in this iron-catalyzed reaction can be achieved through proper choice of the wavelength of irradiation.

| S-EPMC11894668 | biostudies-literature

Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis.

Project description:Bioconjugation technologies have revolutionized the practice of biology and medicine by allowing access to novel biomolecular scaffolds. New methods for residue-selective bioconjugation are highly sought to expand the toolbox for a variety of bioconjugation applications. Herein we report a site-selective methionine bioconjugation protocol that uses photoexcited lumiflavin to generate open-shell intermediates. This reduction-potential-gated strategy enables access to residues unavailable with traditional nucleophilicity-based conjugation methods. To demonstrate the versatility and robustness of this new protocol, we have modified various proteins and further utilized this functional handle to append diverse biological payloads.

| S-EPMC8647115 | biostudies-literature

Photoredox C-H functionalization leads the site-selective phenylalanine bioconjugation.

Project description:Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.

| S-EPMC9643349 | biostudies-literature

Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine.

Project description:The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, is fueling a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and site-specific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction, involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the photocatalytic diselenide contraction transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21st amino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.

| S-EPMC9653470 | biostudies-literature

Synthesis of tertiary alkyl fluorides and chlorides by site-selective nucleophilic ring-opening reaction of α-aryl azetidinium salts.

Project description:Site-selective nucleophilic ring-opening reactions of 2-arylazetidine-2-carboxylic acid ester-derived tetraalkyl ammonium salts 2 with tetrabutylammonium halides (Bu4NX) to give tertiary alkyl halides are successfully demonstrated. For example, a nucleophilic ring-opening reaction of 2-(o-tolyl) derivative 2a with 1.2 equivalents of tetrabutylammonium fluoride (Bu4NF) in THF at 60 °C preferentially proceeded at a more substituted carbon atom (2-position) compared to a less-substituted carbon atom (4-position) and afforded tert-butyl 4-(dimethylamino)-2-fluoro-2-(o-tolyl)butanoate 3aa in 71% yield as the corresponding tertiary alkyl fluoride. This result was applied to synthesize optically active organofluorine compounds starting from commercially available (R)-1-phenylethylamine.

| S-EPMC9044468 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data