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Bioorganic & Medicinal Chemistry Letters Jan 2018The prevalence of 1,3-dipolar cycloadditions of azides and alkynes within both biology and chemistry highlights the utility of these reactions. However, the use of a...
The prevalence of 1,3-dipolar cycloadditions of azides and alkynes within both biology and chemistry highlights the utility of these reactions. However, the use of a copper catalyst can be prohibitive to some applications. Consequently, we have optimized a copper-free microwave-assisted reaction to alleviate the necessity for the copper catalyst. A small array of triazoles was prepared to examine the scope of this approach, and the methodology was translated to a protein context through the use of unnatural amino acids to demonstrate one of the first microwave-mediated bioconjugations involving a full length protein.
Topics: Alkynes; Azides; Cycloaddition Reaction; Microwaves; Models, Molecular; Molecular Structure; Triazoles
PubMed: 29248298
DOI: 10.1016/j.bmcl.2017.12.007 -
Molecules (Basel, Switzerland) May 2024A versatile family of quaternary propargylamines was synthesized employing the KA multicomponent reaction, through the single-step coupling of a number of amines,...
A versatile family of quaternary propargylamines was synthesized employing the KA multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC values for hMAO-B range from 152.1 to 164.7 nM while the IC values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski's rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson's disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.
Topics: Alkynes; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Pargyline; Propylamines; Structure-Activity Relationship; Molecular Structure
PubMed: 38893361
DOI: 10.3390/molecules29112486 -
The Journal of Organic Chemistry Oct 2012The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a highly effective method for the selective incorporation of deuterium atom into the C-5 position of the...
The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a highly effective method for the selective incorporation of deuterium atom into the C-5 position of the 1,2,3-triazole structure. Reactions of alkynes and azides can be conveniently carried out in a biphasic medium of CH(2)Cl(2)/D(2)O, using the CuSO(4)/Na ascorbate system. The mildness of the method renders it applicable to substrates of relatively high complexity, such as nucleosides. Good yields and high levels of deuterium incorporation were observed. A reaction conducted in equimolar H(2)O and D(2)O showed 2.7 times greater incorporation of hydrogen atom as compared to deuterium. This is consistent with the H(+) and D(+) ion concentrations in H(2)O and D(2)O, respectively. With appropriately deuterated precursors, partially to fully deuterated triazoles were assembled where the final deuterium atom was incorporated in the triazole-forming step.
Topics: Alkynes; Azides; Catalysis; Copper; Cyclization; Molecular Structure; Triazoles
PubMed: 23016757
DOI: 10.1021/jo301146j -
Molecules (Basel, Switzerland) Nov 2022The accurate and sensitive detection of biomolecules by surface-enhanced Raman spectroscopy (SERS) is possible, but remains challenging due to the interference from...
The accurate and sensitive detection of biomolecules by surface-enhanced Raman spectroscopy (SERS) is possible, but remains challenging due to the interference from biomolecules in complex samples. Herein, a new SERS sensor is developed for background-free detection of hydrogen peroxide (HO) with an ultralow detection limit (1 × 10 mol/L), using a Raman-silent strategy. The Au microparticles (Au-RSMPs) resembling rose-stones are devised as SERS substrates with a high enhancement effect, and 4-mercaptophenylboronic acid (4-MPBA) is selected as an HO-responsive Raman reporter. Upon the reaction with HO, the phenylboronic group of 4-MPBA was converted to a phenol group, which subsequently reacted with 4-diazonium-phenylalkyne (4-DP), an alkyne-carrying molecule via the azo reaction. The formed product exhibits an intense and sharp SERS signal in the Raman-silent region, avoiding interference of impurities and biomolecules. As a proof-of-concept demonstration, we show that this SERS sensor possesses significant merits towards the determination of HO in terms of broad linear range, low limit of detection, and high selectivity, showing promise for the quantitative analysis of HO in complicated biological samples.
Topics: Hydrogen Peroxide; Spectrum Analysis, Raman; Alkynes
PubMed: 36432018
DOI: 10.3390/molecules27227918 -
Yakugaku Zasshi : Journal of the... 2011The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or an additional allene for construction of various monocyclic and bicyclic ring systems... (Review)
Review
The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or an additional allene for construction of various monocyclic and bicyclic ring systems has been developed. The characteristic features of these methods using allene functionality instead of a simple alkene or alkyne include the reaction mode that originated from the double function as well as the high efficiency for the constructions of medium-sized rings. Furthermore, asymmetric formal synthesis of (+)-nakadomarin A and total synthesis of (+)-fawcettimine and (+)-lycoposerramine-B based on highly stereoselective Pauson-Khand reaction of alkene-alkynes were completed.
Topics: Alkadienes; Alkaloids; Alkenes; Alkynes; Carbolines; Cyclization; Heterocyclic Compounds, 3-Ring; Organic Chemistry Phenomena; Oximes; Stereoisomerism
PubMed: 21963970
DOI: 10.1248/yakushi.131.1437 -
Angewandte Chemie (International Ed. in... Sep 2020The discovery of safe, general, and practical procedures to prepare vinyl fluorides from readily available precursors remains a synthetic challenge. The metal-free...
The discovery of safe, general, and practical procedures to prepare vinyl fluorides from readily available precursors remains a synthetic challenge. The metal-free hydrofluorination of alkynes constitutes an attractive though elusive strategy for their preparation. Introduced here is an inexpensive and easily handled reagent that enables the development of simple and scalable protocols for the regioselective hydrofluorination of alkynes to access both the E and Z isomers of vinyl fluorides. These reaction conditions were suitable for a diverse collection of alkynes, including several highly functionalized pharmaceutical derivatives. Computational and experimental mechanistic studies support C-F bond formation through vinyl cation intermediates, with the E- and Z-hydrofluorination products forming under kinetic and thermodynamic control, respectively.
Topics: Alkynes; Borates; Halogenation; Molecular Structure; Stereoisomerism; Vinyl Compounds
PubMed: 32485005
DOI: 10.1002/anie.202006278 -
Organic Letters Feb 2020Hydrazones readily synthesized from -aminopyrroles or -aminoazoles and aldehydes undergo Rh(III)-catalyzed dual C-H activation and coupling with aryl- and...
Hydrazones readily synthesized from -aminopyrroles or -aminoazoles and aldehydes undergo Rh(III)-catalyzed dual C-H activation and coupling with aryl- and alkyl-substituted alkynes to give pyrrolopyridazines or azolopyridazines, respectively. This transformation represents a rare example of hydrazoyl C-H activation and proceeds without heteroatom functionality to direct C-H activation. Hydrazones derived from aromatic, alkenyl, and aliphatic aldehydes were effective inputs, and tethering the alkyne to the hydrazone enabled annulations to more complex, tricyclic products.
Topics: Alkynes; Azoles; Catalysis; Hydrazones; Molecular Structure; Organometallic Compounds; Pyridazines; Pyrroles; Rhodium; Stereoisomerism
PubMed: 31977232
DOI: 10.1021/acs.orglett.0c00186 -
Journal of the American Chemical Society Apr 2020The marine macrolide chagosensine is supposedly distinguished by a ()-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also...
The marine macrolide chagosensine is supposedly distinguished by a ()-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two -2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The "northern" THF ring and the -configured diol in the "southern" sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives ("Mukaiyama cyclization"), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-γ-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed "Tamaru-type" homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.
Topics: Alkenes; Alkynes; Biological Products; Catalysis; Chemistry Techniques, Synthetic; Cobalt; Cyclization; Furans; Lactones; Macrolides; Oxidation-Reduction; Stereoisomerism
PubMed: 32142305
DOI: 10.1021/jacs.0c01700 -
Scientific Reports Jun 2023A selective synthesis of unsymmetrically functionalized disiloxanes via the subsequent hydrosilylation of internal alkynes in the first step, and alkynes (terminal or...
A selective synthesis of unsymmetrically functionalized disiloxanes via the subsequent hydrosilylation of internal alkynes in the first step, and alkynes (terminal or internal) or 1,3-diynes in the second, with 1,1,3,3-tetramethyldisiloxane (1) is presented for the first time. Using developed approaches performed in a stepwise or one-pot manner a new family of disubstituted disiloxanes was obtained which had previously been inaccessible by other synthetic methods. Moreover, symmetrically functionalized disiloxanes were obtained by direct hydrosilylation of 2 equivalents of terminal or internal alkynes with 1, showing the unique versatility of the hydrosilylation process. Three examples of symmetric disiloxanes were characterized by single crystal X-ray diffraction for the first time. As a result, a wide group of new compounds which can find potential applications as building blocks or coupling agents was obtained and characterized.
Topics: Silanes; Alkynes; Diynes
PubMed: 37353562
DOI: 10.1038/s41598-023-37375-8 -
Molecules (Basel, Switzerland) Dec 2022The present review narrates several reports which deal with the synthesis of fused 1,2,3-triazole containing scaffolds following a sequential multicomponent reaction... (Review)
Review
The present review narrates several reports which deal with the synthesis of fused 1,2,3-triazole containing scaffolds following a sequential multicomponent reaction (MCR)-intramolecular azide-alkyne cycloaddition (IAAC) approach. The reviewed reactions were cleverly designed so as to incorporate azide and alkyne functionalities in the MCR product which was then subjected to IAAC. The review is divided into two sections based on the number of components in the multicomponent reaction. We have aimed at a critical discussion and also have highlighted either advantages or disadvantages of each methodology.
Topics: Cycloaddition Reaction; Azides; Alkynes; Triazoles; Catalysis; Molecular Structure
PubMed: 36615500
DOI: 10.3390/molecules28010308