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Journal of the American Chemical Society Feb 2013Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By...
Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By replacing the C-terminal carboxylate of ubiquitin (Ub) with an alkyne functionality, a selective reaction with the active-site cysteine residue of de-ubiquitinating enzymes was observed. The resulting product was shown to be a quaternary vinyl thioether, as determined by X-ray crystallography. Proteomic analysis of proteins bound to an immobilized Ub alkyne probe confirmed the selectivity toward de-ubiquitinating enzymes. The observed reactivity is not just restricted to propargylated Ub, as highlighted by the selective reaction between caspase-1 (interleukin converting enzyme) and a propargylated peptide derived from IL-1β, a caspase-1 substrate.
Topics: Alkynes; Catalytic Domain; Cysteine; Peptide Hydrolases
PubMed: 23387960
DOI: 10.1021/ja309802n -
Chemical Communications (Cambridge,... Oct 2017Sydnones are among the most popular mesoionic compounds studied so far for cycloaddition reactions. However, despite their good chemical stability and versatility, only... (Review)
Review
Sydnones are among the most popular mesoionic compounds studied so far for cycloaddition reactions. However, despite their good chemical stability and versatility, only a limited number of research groups have worked on their chemistry and use in organic synthesis. This feature article aims at providing an overview of the most recent developments in sydnone-alkyne cycloadditions, with particular attention on the strategies that allow us to achieving high regiocontrol and milder reaction conditions. The recent discovery that this dipole is able to undergo click and biorthogonal reactions with cycloalkynes may stimulate renewed interest from the scientific community. Given the high potential and flexibility of this family of mesoionics, we believe that major developments are to be expected both in terms of organic synthetic methodologies and biorthogonal chemistry applications in the field of chemical biology.
Topics: Alkynes; Click Chemistry; Cycloaddition Reaction; Sydnones
PubMed: 28959814
DOI: 10.1039/c7cc06405e -
Chemical Reviews Aug 2022Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. While there are efforts at catalyst design using computation/artificial... (Review)
Review
Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. While there are efforts at catalyst design using computation/artificial intelligence, at its core, synthetic chemistry is an experimental science. This review overviews biomacromolecule-assisted screening methods and the follow-on elaboration of chemistry so discovered. All three types of biomacromolecules discussed─enzymes, antibodies, and nucleic acids─have been used as "sensors" to provide a readout on product chirality exploiting their native chirality. Enzymatic sensing methods yield both UV-spectrophotometric and visible, colorimetric readouts. Antibody sensors provide direct fluorescent readout upon analyte binding in some cases or provide for cat-ELISA (Enzyme-Linked ImmunoSorbent Assay)-type readouts. DNA biomacromolecule-assisted screening allows for templation to facilitate reaction discovery, bimolecular reactions into a pseudo-unimolecular format. In addition, the ability to use DNA-encoded libraries permits the barcoding of reactants. All three types of biomacromolecule-based screens afford high sensitivity and selectivity. Among the chemical transformations discovered by enzymatic screening methods are the first Ni(0)-mediated asymmetric allylic amination and a new thiocyanopalladation/carbocyclization transformation in which both C-SCN and C-C bonds are fashioned sequentially. Cat-ELISA screening has identified new classes of sydnone-alkyne cycloadditions, and DNA-encoded screening has been exploited to uncover interesting oxidative Pd-mediated amido-alkyne/alkene coupling reactions.
Topics: Alkynes; Amination; Artificial Intelligence; Catalysis; DNA
PubMed: 35904776
DOI: 10.1021/acs.chemrev.2c00213 -
Current Medicinal Chemistry 2023Sydnones are among the most well-known mesoionic compounds. Since their synthesis in 1935 by Earl and Mecknay, numerous researches have shown that the chemical behavior,...
Sydnones are among the most well-known mesoionic compounds. Since their synthesis in 1935 by Earl and Mecknay, numerous researches have shown that the chemical behavior, physical and biological properties of sydnones make them the most useful compounds in organic chemistry. Sydnones undergo thermal 1,3-dipolar cycloaddition reaction with dipolarophiles (alkynes or alkenes) to give exclusively derivatives containing a pyrazole moiety exhibiting numerous applications, such as pharmaceuticals and agrochemicals. However, the sydnone cycloaddition reaction with alkynes requires harsh conditions, like high temperatures and long reaction times, giving poor regioselectivity to the resulting products. To overcome these constraints, new reactions named CuSAC (Copper- Catalyzed Sydnone-Alkyne Cycloaddition) and SPSAC (Strain-Promoted Sydnone- Alkyne Cycloaddition) have been developed, leading to pyrazoles with interesting constant kinetics.
Topics: Humans; Alkynes; Sydnones; Cycloaddition Reaction; Copper
PubMed: 35726409
DOI: 10.2174/0929867329666220620123050 -
Marine Drugs Nov 2016Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine... (Review)
Review
Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine mollusks. This review has presented 66 peptides, which covers over 90% marine peptides with terminal alkynyl fatty acyl units. In fact, more than 90% of these peptides described in the literature are of cyanobacterial origin. Interestingly, all the linear peptides featured with terminal alkyne were solely discovered from marine cyanobacteria. The objective of this article is to provide an overview on the types, structural characterization of these unusual terminal alkynyl fatty acyl units, as well as the sources and biological functions of their composed peptides. Many of these peptides have a variety of biological activities, including antitumor, antibacterial, antimalarial, etc. Further, we have also discussed the evident biosynthetic origin responsible for formation of terminal alkynes of natural PKS (polyketide synthase)/NRPS (nonribosome peptide synthetase) hybrids.
Topics: Alkynes; Aquatic Organisms; Biological Products; Cyanobacteria; Humans; Peptide Synthases; Peptides; Polyketide Synthases
PubMed: 27886049
DOI: 10.3390/md14110216 -
Angewandte Chemie (International Ed. in... May 2014Iron catalysis has been developed for the intermolecular 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate scope and high...
Iron catalysis has been developed for the intermolecular 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate scope and high functional-group tolerance. A variety of perfluoroalkyl iodides including CF3 I can be employed. The resulting perfluoroalkylated alkyl and alkenyl iodides can be further functionalized by cross-coupling reactions. This methodology provides a straightforward and streamlined access to perfluoroalkylated organic molecules.
Topics: Alkenes; Alkynes; Catalysis; Iodides; Iron
PubMed: 24683156
DOI: 10.1002/anie.201402511 -
Methods in Molecular Biology (Clifton,... 2023Click chemistry, and particularly azide-alkyne cycloaddition, represents one of the principal bioconjugation strategies that can be used to conveniently attach various...
Click chemistry, and particularly azide-alkyne cycloaddition, represents one of the principal bioconjugation strategies that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields were obtained in the presence of bathophenanthrolinedisulphonate, a water-soluble copper-ion chelator, acting as catalyst. No vesicle leakage was triggered by this conjugation reaction, and the coupled mannose ligands were exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this type of conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent this constraint, an example of alternate copper-free azide-alkyne click reaction has been developed, and it was applied to the anchoring of a biotin moiety that was fully functional and could be therefore quantified. Molecular tools and results are presented here.
Topics: Liposomes; Click Chemistry; Azides; Catalysis; Alkynes; Ligands; Cycloaddition Reaction
PubMed: 36781760
DOI: 10.1007/978-1-0716-2954-3_15 -
The Journal of Organic Chemistry Sep 2017SNO-OCTs are eight-membered heterocyclic alkynes that have fast rates of reactivity with 1,3-dipoles. In contrast to many other reported cycloalkynes, SNO-OCTs contain...
SNO-OCTs are eight-membered heterocyclic alkynes that have fast rates of reactivity with 1,3-dipoles. In contrast to many other reported cycloalkynes, SNO-OCTs contain multiple sites for derivatization, display stability under a variety of common reaction conditions, and offer the opportunity for strain-induced ring-opening following the initial reaction of the alkyne moiety. In this paper, we describe how the unique features of SNO-OCTs can be employed to modify an oxime-bearing styrene copolymer and introduce an array of polar functionalities into the polymer. This can be achieved through both the addition of SNO-OCT to the polymer, as well as in the subsequent opening of the sulfamate ring once it has been installed in the polymer.
Topics: Alkynes; Heterocyclic Compounds; Nitrogen; Oxygen; Polymerization; Polymers; Sulfur
PubMed: 28795808
DOI: 10.1021/acs.joc.7b01506 -
Organic & Biomolecular Chemistry Jul 2022Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-]pyrazol-4(2)-ones or...
Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-]pyrazol-4(2)-ones or 2,5-dihydro-4-pyrazolo[4,3-]quinolin-4-ones Cu(II)-promoted oxidative cascade C-C/C-N bond formation. This protocol has the advantages of atom economy and good functional group tolerance. The primary mechanism studies indicate that the reaction involves a free-radical process as well as terminal alkyne C-H activation.
Topics: Alkynes; Oxidation-Reduction; Oxidative Stress
PubMed: 35792135
DOI: 10.1039/d2ob00639a -
Bioorganic & Medicinal Chemistry Jun 2009An overview is given of the significance of alkyne derivatives in crop protection chemistry. The main herbicidally, fungicidally, insecticidally and acaricidally active... (Review)
Review
An overview is given of the significance of alkyne derivatives in crop protection chemistry. The main herbicidally, fungicidally, insecticidally and acaricidally active alkyne classes are presented, together with their synthetic routes, their mode of action and their biological efficacies. Also the importance of alkynes as intermediates in the preparation of agrochemicals is demonstrated.
Topics: Agrochemicals; Alkynes; Antifungal Agents; Crops, Agricultural; Herbicides; Insecticides
PubMed: 19059785
DOI: 10.1016/j.bmc.2008.11.037