616 results on '"Oxocarbenium"'
Search Results
2. Brønsted Acid Catalyzed Stereoselective Polymerization of Vinyl Ethers
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Travis P. Varner, Frank A. Leibfarth, Paige E Jacky, Aaron J. Teator, Phil C. Knutson, and Caleb T Kozuszek
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organic chemicals ,technology, industry, and agriculture ,Oxocarbenium ,Chain transfer ,macromolecular substances ,General Chemistry ,Vinyl ether ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Monomer ,Polymerization ,chemistry ,Polymer chemistry ,medicine ,Lewis acids and bases ,Brønsted–Lowry acid–base theory ,medicine.drug - Abstract
Isotactic poly(vinyl ether)s (PVEs) have recently been identified as a new class of semicrystalline thermoplastics with a valuable combination of mechanical and interfacial properties. Currently, methods to synthesize isotactic PVEs are limited to strong Lewis acids that require a high catalyst loading and limit the accessible scope of monomer substrates for polymerization. Here, we demonstrate the first Bronsted acid catalyzed stereoselective polymerization of vinyl ethers. A single-component imidodiphosphorimidate catalyst exhibits a sufficiently low pKa to initiate vinyl ether polymerization and acts as a chiral conjugate base to direct the stereochemistry of monomer addition to the oxocarbenium ion reactive chain end. This Bronsted acid catalyzed stereoselective polymerization enabled an expanded substrate scope compared to previous methods, the use of chain transfer agents to lower catalyst loading, and the capability to recycle the catalyst for multiple polymerizations.
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- 2021
3. Enantioselective Transfer Hydrogenation of Oxocarbenium Ions Enables Asymmetric Access to α-Substituted 1,3-Dihydroisobenzofurans
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Kuiyong Jia, Likai Zhou, Xigong Liu, and Lei Liu
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chemistry.chemical_compound ,Chemistry ,Organic Chemistry ,Acetal ,Enantioselective synthesis ,Oxocarbenium ,Transfer hydrogenation ,Combinatorial chemistry ,Catalysis ,Ion - Abstract
Reported here is an efficient enantioselective transfer hydrogenation of cyclic oxocarbenium ions generated in situ through collapse of the corresponding acetal substrates. The asymmetric approach provides straightforward access to a variety of chiral α-aryl substituted 1,3-dihydroisobenzofurans in high yields with excellent enantioselectivities. α-Alkynyl substituted 1,3-dihydroisobenzofurans were also proved to be suitable substrates. In addition, when the reaction was performed at gram scale, the desired product was obtained in good yields with excellent enantioselectivity.
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- 2021
4. Brønsted Acid Catalyzed Oxocarbenium-Olefin Metathesis/Rearrangements of 1H-Isochromene Acetals with Vinyl Diazo Compounds
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Michael P. Doyle, Hadi D. Arman, Haifeng Zheng, Kan Wang, and Luca De Angelis
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chemistry.chemical_classification ,Alkene ,Oxocarbenium ,General Chemistry ,Metathesis ,Biochemistry ,Medicinal chemistry ,Catalysis ,Cycloaddition ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Diazo ,Selectivity ,Brønsted–Lowry acid–base theory - Abstract
An oxocarbenium-olefin cross metathesis occurs during Bronsted acid catalyzed reactions of 1H-isochromene acetals with vinyl diazo compounds. Formally a carbonyl-alkene [2 + 2]-cyclization between isobenzopyrylium ions and the vinyl group of vinyl diazoesters, the retro-[2 + 2] cycloaddition produces a tethered alkene and a vinyl diazonium ion that, upon loss of dinitrogen, undergoes a highly selective carbocationic cascade rearrangements to diverse products whose formation is controlled by reactant substituents. Polysubstituted benzobicyclo[3.3.1]oxocines, benzobicyclo[3.2.2]oxepines, benzobicyclopropane, and naphthalenes are obtained in good to excellent yields and selectivities. Furthermore, isotopic tracer and control experiments shed light on the oxocarbenium-olefin metathesis/rearrangement process as well as on the origin of the interesting substituent-dependent selectivity.
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- 2021
5. Size- and Shape-Selective Catalysis with a Functionalized Self-Assembled Cage Host
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Bryce da Camara, Courtney Ngai, Connor Z. Woods, and Richard J. Hooley
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chemistry.chemical_classification ,Carboxylic acid ,Organic Chemistry ,Carboxylic Acids ,Oxocarbenium ,Substrate (chemistry) ,Carbocation ,Photochemistry ,Catalysis ,Organic Chemistry Phenomena ,chemistry ,Nucleophilic substitution ,Reactivity (chemistry) ,Selectivity - Abstract
A self-assembled Fe4L6 cage with internally oriented carboxylic acid functions was shown to catalyze a variety of dissociative nucleophilic substitution reactions that proceed via oxocarbenium ion or carbocation intermediates. The catalytic behavior of the cage was compared to that of other small acid catalysts, which illustrated large differences in reactivity of the cage-catalyzed reactions, dependent on the structure of the substrate. For example, only a 5% cage confers a 1000-fold rate acceleration of the thioetherification of vinyldiphenylmethanol when compared to the rate with free carboxylic acid surrogates but only a 52-fold acceleration in the formation of small thioacetals. Multiple factors control the variable reactivity in the host, including substrate inhibition, binding affinity, and accessibility of reactive groups once bound. Simple effective concentration increases or the overall charge of the cage does not explain the variations in reactivity shown by highly similar reactants in the host: small differences in structure can have large effects on reactivity. Reaction of large spherical guests is highly dependent on substitution, whereas flat guests are almost unaffected by size and shape differences. The cage is a promiscuous catalyst but has strong selectivity for particular substrate shapes, reminiscent of enzymatic activity.
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- 2021
6. Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis
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Ahmed Anwar Dezaye, Sirwan T. Othman, Giuseppe Zanoni, Alessio Porta, Debora Chiodi, and Emanuele Casali
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Oxazolidine ,Anomer ,Glycosylation ,010405 organic chemistry ,Chemistry ,Hydride ,Organic Chemistry ,Oxocarbenium ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Enol ,Pyrrolidine ,Article ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Rhenium ,Nucleophile ,Alcohols ,Ethers - Abstract
A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.
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- 2021
7. Role of hydrogen bond alternation and charge transfer states in photoactivation of the Orange Carotenoid Protein
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Tomáš Polívka, Miroslav Kloz, Nikolai N. Sluchanko, Dmitry V. Zlenko, Igor A. Yaroshevich, Ekaterina A. Slutskaya, Alexey Stepanov, Dmitry Khakhulin, Dmitry A. Cherepanov, Ivan Gushchin, Timofey S. Gostev, Vladimir V. Poddubnyy, Alina Remeeva, Victor A. Nadtochenko, Thomas Friedrich, Eugene G. Maksimov, Viacheslav S. Botnarevskii, Fedor E. Gostev, Valentin Gordeliy, Ivan V. Shelaev, Kirill Kovalev, Yury B. Slonimskiy, Mikhail P. Kirpichnikov, Vladimir Z. Paschenko, and Andrew B. Rubin
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0301 basic medicine ,Models, Molecular ,Absorption spectroscopy ,Photochemistry ,Protein Conformation ,QH301-705.5 ,Oxocarbenium ,Medicine (miscellaneous) ,Protonation ,010402 general chemistry ,01 natural sciences ,Chemical reaction ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Bacterial Proteins ,ddc:570 ,Biology (General) ,X-ray crystallography ,Crystallography ,Orange carotenoid protein ,Hydrogen bond ,Chemistry ,Proteins ,Hydrogen Bonding ,Molecular biophysics ,Carotenoids ,0104 chemical sciences ,Kinetics ,030104 developmental biology ,Excited state ,Yield (chemistry) ,General Agricultural and Biological Sciences - Abstract
Communications biology 4(1), 539 (1-13) (2021). doi:10.1038/s42003-021-02022-3, Here, we propose a possible photoactivation mechanism of a 35-kDa blue light-triggered photoreceptor, the Orange Carotenoid Protein (OCP), suggesting that the reaction involves the transient formation of a protonated ketocarotenoid (oxocarbenium cation) state. Taking advantage of engineering an OCP variant carrying the Y201W mutation, which shows superior spectroscopic and structural properties, it is shown that the presence of Trp201 augments the impact of one critical H-bond between the ketocarotenoid and the protein. This confers an unprecedented homogeneity of the dark-adapted OCP state and substantially increases the yield of the excited photoproduct S*, which is important for the productive photocycle to proceed. A 1.37 �� crystal structure of OCP Y201W combined with femtosecond time-resolved absorption spectroscopy, kinetic analysis, and deconvolution of the spectral intermediates, as well as extensive quantum chemical calculations incorporating the effect of the local electric field, highlighted the role of charge-transfer states during OCP photoconversion., Published by Springer Nature, London
- Published
- 2021
8. Nickel(II)-catalyzed asymmetric alkylation of acyclic oxocarbenium ions with carboxylic acid derivatives
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Gang Wang, Xuan Liu, Lei Liu, and Pengbo Ye
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chemistry.chemical_classification ,Carboxylic acid ,Oxocarbenium ,chemistry.chemical_element ,Compatibility (geochemistry) ,02 engineering and technology ,General Chemistry ,Alkylation ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,Ion ,chemistry.chemical_compound ,Nickel ,chemistry ,Functional group ,0210 nano-technology - Abstract
A nickel(II)-catalyzed asymmetric alkylation of acyclic oxocarbenium ions generated in situ from corresponding acetals with carboxylic acid derivatives to prepare β-alkoxyl carbonyl moieties with diverse α-substituents has been disclosed. The method exhibited broad scope of acetals and carboxylic acid derivatives with excellent enantioselectivity and good functional group compatibility, and can be conducted in a gram-scale without obvious loss of efficiency.
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- 2021
9. Glycosylation by Alkyne Activation of the 2-O-Substituted Propargyl Group in a β-Phenylthioglucoside with a 5 S 1 Conformation
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Kazutada Ikeuchi, Hidetoshi Yamada, Daiki Ikuta, and Shintaro Matsumoto
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chemistry.chemical_classification ,Glycosylation ,Anomer ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Glycosyl acceptor ,Oxocarbenium ,Substituent ,Alkyne ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Propargyl ,Glycosyl donor - Abstract
Generally, glycosylation reactions activate an anomeric substituent in a glycosyl donor to generate an oxocarbenium ion intermediate. Here we report a novel glycosylation reaction triggered by the activation of a 2-O-substituted propargyl group in a 3,6-O-1,1′-[(ethane-1,2-diyl)bibenzene-2,2′-bis(methylene)]-β-thioglucoside. This reaction proceeds through a cationic Au(I)-mediated intramolecular migration of the anomeric substituent onto the alkyne moiety of the propargyl group, followed by α-attack by the hydroxy group in the glycosyl acceptor on the oxocarbenium ion. The migration of the anomeric group occurs selectively through a 6-exo-dig pathway. The 2-(phenylsulfanyl)prop-2-en-1-yl group produced during the glycosylation is removable under conditions similar to those used for removing an allyl group. This reaction will be developed for further applications in orthogonal oligosaccharide synthesis.
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- 2021
10. Cooperation of Cis Vicinal Acceptors for Donor–Acceptor Cyclopropane Activation: TfOH-Promoted Ring-Opening/Aryl Shift Rearrangement to 3- and 5-Ylidenebutenolides
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Qinyuan Luo, Sunewang R. Wang, Jiru Shao, and Hongyan Bi
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Bicyclic molecule ,Chemistry ,Aryl ,Organic Chemistry ,Oxocarbenium ,Biochemistry ,Medicinal chemistry ,Cyclopropane ,chemistry.chemical_compound ,Deprotonation ,Physical and Theoretical Chemistry ,Vicinal ,Acyl group ,Cis–trans isomerism - Abstract
A convenient route to 3- and 5-ylidenebutenolides from readily available cis-2-acylcyclopropane-1-carboxylates is described. Upon exposure to TfOH, synergistic activation of the vicinal acceptors in cis-2-acylcyclopropane-1-carboxylates generates highly strained bicyclic oxocarbenium ion intermediates, which undergo the ring-opening/aryl shift/deprotonation cascade process to form the 3- or 5-ylidenebutenolides depending on the acyl group. On the other hand, the corresponding trans isomers, from which it is difficult to form such oxocarbenium ions, are inactive under the same conditions.
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- 2021
11. Selective aldehyde reductions in neutral water catalysed by encapsulation in a supramolecular cage
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Mark D. Symes, Michael A. Shipman, Stephen Sproules, Avishek Paul, and Dolapo Y. Onabule
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chemistry.chemical_classification ,Sodium cyanoborohydride ,Oxocarbenium ,Supramolecular chemistry ,General Chemistry ,Reaction intermediate ,Aldehyde ,Combinatorial chemistry ,Catalysis ,Chemistry ,chemistry.chemical_compound ,chemistry ,Coordination cage ,Reactivity (chemistry) - Abstract
The enhancement of reactivity inside supramolecular coordination cages has many analogies to the mode of action of enzymes, and continues to inspire the design of new catalysts for a range of reactions. However, despite being a near-ubiquitous class of reactions in organic chemistry, enhancement of the reduction of carbonyls to their corresponding alcohols remains very much underexplored in supramolecular coordination cages. Herein, we show that encapsulation of small aromatic aldehydes inside a supramolecular coordination cage allows the reduction of these aldehydes with the mild reducing agent sodium cyanoborohydride to proceed with high selectivity (ketones and esters are not reduced) and in good yields. In the absence of the cage, low pH conditions are essential for any appreciable conversion of the aldehydes to the alcohols. In contrast, the specific microenvironment inside the cage allows this reaction to proceed in bulk solution that is pH-neutral, or even basic. We propose that the cage acts to stabilise the protonated oxocarbenium ion reaction intermediates (enhancing aldehyde reactivity) whilst simultaneously favouring the encapsulation and reduction of smaller aldehydes (which fit more easily inside the cage). Such dual action (enhancement of reactivity and size-selectivity) is reminiscent of the mode of operation of natural enzymes and highlights the tremendous promise of cage architectures as selective catalysts., Herein, we use a supramolecular coordination cage as a catalyst for the reduction of aldehydes to the corresponding alcohols using a weak hydride donor in neutral water, with a mode of action reminiscent of natural enzymes.
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- 2021
12. En Route to the Transformation of Glycoscience: A Chemist’s Perspective on Internal and External Crossroads in Glycochemistry
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David Crich
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Glycosylation ,Chemistry ,Carbohydrate chemistry ,Chemistry, Pharmaceutical ,media_common.quotation_subject ,Carbohydrates ,Chemistry, Organic ,Oxocarbenium ,Stereoisomerism ,General Chemistry ,010402 general chemistry ,Chemist ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,0104 chemical sciences ,Epistemology ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Ingenuity ,Organic synthesis ,media_common - Abstract
Carbohydrate chemistry is an essential component of the glycosciences and is fundamental to their progress. This perspective takes the position that carbohydrate chemistry, or glycochemistry, has reached three crossroads on the path to the transformation of the glycosciences, and illustrates them with examples from the author’s and other laboratories. The first of these potential inflexion points concerns the mechanism of the glycosylation reaction and the role of protecting groups. It is argued that the experimental evidence supports bimolecular S(N)2-like mechanisms for typical glycosylation reactions over unimolecular ones involving stereoselective attack on naked glycosyl oxocarbenium ions. Similarly, it is argued that the experimental evidence does not support long range stereodirecting participation of remote esters through bridged bicyclic dioxacarbenium ions in organic solution in the presence of typical counterions. Rational design and improvement of glycosylation reactions must take into account the role of the counterion and of concentration. A second crossroads is that between mainstream organic chemistry and glycan synthesis. The case is made that the only real difference between glycan and organic synthesis is the formation of C-O rather than C-C bonds, with diastereocontrol, strategy, tactics and elegance being of critical importance in both areas: mainstream organic chemists should feel comfortable taking this fork in the road, just as carbohydrate chemists should travelling in the opposite direction. A third crossroads is that between carbohydrate chemistry and medicinal chemistry, where there are equally many opportunities for traffic in either direction. The glycosciences have advanced enormously in the last decade or so, but the creativity, input and ingenuity of scientists from all fields is needed to address the many sophisticated challenges that remain, not the least of which is the development of a broader and more general array of stereospecific glycosylation reactions.
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- 2020
13. The Role of Fluorine in Glycomimetic Drug Design
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Rachel Hevey
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Drug ,Glycan ,Halogenation ,media_common.quotation_subject ,Oxocarbenium ,010402 general chemistry ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,Biomimetic Materials ,Biomimetics ,Polysaccharides ,Glycomimetic ,Glycosides ,media_common ,Binding affinities ,biology ,010405 organic chemistry ,Drug discovery ,Organic Chemistry ,Carbasugars ,Fluorine ,General Chemistry ,Combinatorial chemistry ,0104 chemical sciences ,3. Good health ,chemistry ,Drug Design ,biology.protein ,Bioisostere - Abstract
Glycans are well established to play important roles at various stages of infection and disease, and ways to modulate these interactions have been sought as novel therapies. The use of native glycan structures has met with limited success, which can be attributed to their characteristic high polarity (e.g., low binding affinities) and inherently poor pharmacokinetic properties (e.g., short drug-target residence times, rapid renal excretion), leading to the development of 'glycomimetics'. Fluorinated drugs have become increasingly common over recent decades, with fluorinated glycomimetics offering some unique advantages. Deoxyfluorination maintains certain electrostatic interactions, while concomitantly reducing net polarity through 'polar hydrophobicity', improving residence times and binding affinities. Fluorination destabilizes the oxocarbenium transition state associated with metabolic degradation, and can restore exo- and endo-anomeric effects in C-glycosides and carbasugars. Lastly, it has shown great utility in radiotracer development and enhancement of antigenicity in glycan-based vaccines. Owing to synthetic challenges, fluorinated glycomimetics have been somewhat underutilized to date, but methodological improvements will advance their use in glycomimetic drugs.
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- 2020
14. Orthoester in Cyclodehydration of Carbamate-Protected Amino Alcohols under Acidic Conditions.
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Heemin Park, Yongseok Kwon, Jae Eui Shin, Woo-Jung Kim, Soonho Hwang, Seokwoo Lee, and Sanghee Kim
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HETEROCYCLIC compounds , *CARBAMATES , *AMINO alcohols , *NUCLEOPHILIC reactions , *RING formation (Chemistry) , *LEWIS acids - Abstract
The first acid-promoted reaction system to form azaheterocycles from N-carbamate-protected amino alcohols is described. The reaction involves the activation of the hydroxyl group via the use of orthoesters. Despite the reduced nucleophilicity of carbamate nitrogen, this reaction system provides several types of pyrrolidines and piperidines in good to high yields. Using this protocol, prolinol derivatives can also be synthesized from carbamate-protected amino diols with regioand stereoselectivity. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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15. α-Tertiary Dialkyl Ether Synthesis via Reductive Photocatalytic α-Functionalization of Alkyl Enol Ethers
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Darren J. Dixon, Thomas Rossolini, Jamie A. Leitch, and Tatiana Rogova
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chemistry.chemical_classification ,Alkene ,010405 organic chemistry ,Chemistry ,Oxocarbenium ,Photoredox catalysis ,Ether ,General Chemistry ,Conjugated system ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Enol ,Catalysis ,0104 chemical sciences ,Williamson ether synthesis ,chemistry.chemical_compound ,Polymer chemistry ,Enol ether ,Alkyl - Abstract
The photocatalytic construction of C(sp3)-rich α-tertiary dialkyl ethers through the reductive α-functionalization of alkyl enol ether substrates with conjugated alkenes in the presence of a Hantzsch ester terminal reductant under blue LED irradiation, is described. Pivoting on oxocarbenium ion generation via an initial TMSCl-facilitated protic activation of the enol ether substrate, subsequent single electron transfer delivers the key nucleophilic α-oxy tertiary radical capable of productively combining with a variety of alkene substrates. The new reductive functionalization strategy was simple to perform, efficient, broad in scope with respect to both alkene acceptor and enol ether donor fragments and delivered a wide range of complex α-tertiary dialkyl ether architectures.
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- 2020
16. Glycoside Hydrolases Restrict the Side Chain Conformation of Their Substrates To Gain Additional Transition State Stabilization
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David Crich and Jonathan C. K. Quirke
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Models, Molecular ,1-Deoxynojirimycin ,Glycosylation ,Anomer ,Glycoside Hydrolases ,Stereochemistry ,Carbohydrates ,Oxocarbenium ,Crystallography, X-Ray ,Ligands ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Phase Transition ,Article ,Catalysis ,chemistry.chemical_compound ,Hydrolysis ,Colloid and Surface Chemistry ,Carbohydrate Conformation ,Side chain ,Reactivity (chemistry) ,Glycoside hydrolase ,Enzyme Inhibitors ,Protein Stability ,Indolizines ,General Chemistry ,Carbohydrate ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry ,Neuraminic Acids ,lipids (amino acids, peptides, and proteins) ,Protein Binding - Abstract
Carbohydrate side chain conformation confers a significant influence on reactivity during glycosylation and anomeric bond hydrolysis due to stabilization of the oxocarbenium intermediate or oxocarbenium-like transition state. By analysis of 513 pyranoside-bound glycoside hydrolase (GH) crystal structures, we determine that most glucosidases and β-mannosidases preferentially bind their substrates in the most reactive gauche,gauche (gg) conformation, thereby maximizing stabilization of the corresponding oxocarbenium ion-like transition state during hydrolysis. α-Galactoside hydrolases mostly show a preference for the second most activating gauche,trans (gt) conformation to avoid the energy penalty that would arise from imposing the gg conformation on galacto-configured ligands. These preferences stand in stark contrast to the side chain populations observed for these sugars both in free solution and bound to non-hydrolytic proteins, where for the most part a much greater diversity of side chain conformations is observed. Analysis of sequences of GH-ligand complexes reveals that side chain restriction begins with the enzyme-substrate complex and persists through the transition state until release of the hydrolysis product, despite changes in ring conformation along the reaction coordinate. This work will inform the design of new generations of glycosidase inhibitors with restricted side chains that confer higher selectivity and/or affinity.
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- 2020
17. Synthesis of Seven Membered Oxacycles: Recent Developments and New Approaches
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Victoria Sinka, Juan I. Padrón, Víctor S. Martín, Daniel A. Cruz, Ministerio de Ciencia, Innovación y Universidades (España), Gobierno de Canarias, Agencia Estatal de Investigación (España), and Cabildo de Tenerife
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Oxepine ,010405 organic chemistry ,Organic Chemistry ,Oxocarbenium ,Carbocation ,010402 general chemistry ,Ring (chemistry) ,Metathesis ,01 natural sciences ,0104 chemical sciences ,Seven‐membered rings ,Oxepane ,chemistry.chemical_compound ,Ring-closing metathesis ,chemistry ,Computational chemistry ,Oxepene ,Physical and Theoretical Chemistry ,Conjugate - Abstract
This minireview focuses on recent advances in the synthesis of seven‐membered ring oxacycles, whether saturated, unsaturated, fused or isolated. We cover a remarkable variety of strategies and methods developed during the past two decades, based mainly on cyclizations, ring‐closing metathesis, conjugate additions, and ring expansions. The cyclizations can be generated directly or triggered through an oxocarbenium ion, carbocation or iminium‐type species. Also discussed are ring‐closing metatheses and conjugate additions, in which the precursor has the functionalities and correct stereochemistry of the final seven‐membered ring oxacycle. Finally, examples of ring expansions are described, predominantly involving cyclopropanes and epoxides. These cases include reactions governed by the intermediate species and others, where the precursor holds the stereochemical information for the final oxacycle., This research was supported by the Ministerio de Ciencia, Innovación y Universidades (MCIU), la Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER) and ACIISI (Gobierno de Canarias) (PGC2018‐094503‐B–C22 and ProID2017010118). V. S. thanks the Spanish MCIU for an F.P.U. fellowship. D. A. C. thanks the Cabildo de Tenerife for a postdoctoral Agustín de Betancourt contract. The manuscript was edited by Guido Jones, also funded currently by Cabildo de Tenerife under the TFinnova Program, supported by MEDI and FDCAN.
- Published
- 2020
18. Enantioselective Allylation of Oxocarbenium Ions Catalyzed by Bi(OAc)3/Chiral Phosphoric Acid
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Jin-Pei Cheng, Hanliang Zheng, Xin Li, Yu-Liang Pan, Jie Wang, and Chen Yang
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010405 organic chemistry ,Oxocarbenium ,Enantioselective synthesis ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Ion ,chemistry.chemical_compound ,chemistry ,Molecule ,Phosphoric acid - Abstract
Phthalides as the crucial core skeletons are found extensively in natural products and biological active molecules. Herein we disclose an asymmetric allylation of 3-hydroxyisobenzofuran-1(3H)-ones ...
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- 2020
19. Mannosidase mechanism: at the intersection of conformation and catalysis
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Spencer J. Williams, Alexandra Males, Gideon J. Davies, and Carme Rovira
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Mannosidase ,0303 health sciences ,Stereochemistry ,Cyclohexane conformation ,Molecular Conformation ,Oxocarbenium ,Mannose ,Sequence (biology) ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Structural Biology ,Biocatalysis ,Mannosidases ,Glycoside hydrolase ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Mannosidases are a diverse group of enzymes that are important in the biological processing of mannose-containing polysaccharides and complex glycoconjugates. They are found in 12 of the >160 sequence-based glycosidase families. We discuss evidence that nature has evolved a small set of common mechanisms that unite almost all of these mannosidase families. Broadly, mannosidases (and the closely related rhamnosidases) perform catalysis through just two conformations of the oxocarbenium ion-like transition state: a B2,5 (or enantiomeric 2,5B) boat and a 3H4 half-chair. This extends to a new family (GT108) of GDPMan-dependent β-1,2-mannosyltransferases/phosphorylases that perform mannosyl transfer through a boat conformation as well as some mannosidases that are metalloenzymes and require divalent cations for catalysis. Yet, among this commonality lies diversity. New evidence shows that one unique family (GH99) of mannosidases use an unusual mechanism involving anchimeric assistance via a 1,2-anhydro sugar (epoxide) intermediate.
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- 2020
20. Silicon‐Derived Singlet Nucleophilic Carbene Reagents in Organic Synthesis
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Daniel L. Priebbenow
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Silicon ,010405 organic chemistry ,Chemistry ,Oxocarbenium ,chemistry.chemical_element ,General Chemistry ,Brook rearrangement ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,chemistry.chemical_compound ,Nucleophile ,Reactivity (chemistry) ,Organic synthesis ,Singlet state ,Carbene - Abstract
Over fifty years ago, the 1,2-rearrangement of acylsilanes was first described by Adrian Brook and co-workers. This rearrangement (now termed the Brook rearrangement) yields reactive silicon-based singlet nucleophilic carbene (SNC) intermediates that participate in a variety of chemical transformations including 1,2-carbonyl addition, 1,4-addition to electron-deficient unsaturated bonds and insertion into C−H and O−H bonds. This review aims to cover the historical literature and recent advances with regard to these valuable silicon-based reagents and highlight additional aspects related to the intriguing reactivity of both the carbene and oxocarbenium intermediates. (Figure presented.).
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- 2020
21. Alkynyl Prins and Alkynyl Aza-Prins Annulations: Scope and Synthetic Applications
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Connor Holt, Shukree Abdul-Rashed, and Alison J. Frontier
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chemistry.chemical_classification ,Annulation ,Pericyclic reaction ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Oxocarbenium ,Alkyne ,Iminium ,Prins reaction ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Nucleophile ,Electrophile - Abstract
This review focuses on alkynyl Prins and alkynyl aza-Prins cyclization processes, which involve intramolecular coupling of an alkyne with either an oxocarbenium or iminium electrophile. The oxocarbenium or iminium species can be generated through condensation- or elimination-type processes, to achieve an overall bimolecular annulation that enables the synthesis of both oxygen- and nitrogen-containing saturated heterocycles with different ring sizes and substitution patterns. Also discussed are cascade processes in which alkynyl Prins heterocyclic adducts react to trigger subsequent pericyclic reactions, including [4+2] cycloadditions and Nazarov electrocyclizations, to rapidly construct complex small molecules. Finally, examples of the use of alkynyl Prins and alkynyl aza-Prins reactions in the synthesis of natural products are described. The review covers the literature through the end of 2019.1 Introduction1.1 Alkyne-Carbonyl Coupling Pathways1.2 Coupling/Cyclization Cascades Using the Alkynyl Prins Reaction2 Alkynyl Prins Annulation (Oxocarbenium Electrophiles)2.1 Early Work2.2 Halide as Terminal Nucleophile2.3 Oxygen as Terminal Nucleophile2.4 Arene as Terminal Nucleophile (Intermolecular)2.5 Arene Terminal Nucleophile (Intramolecular)2.6 Cyclizations Terminated by Elimination3 Synthetic Utility of Alkynyl Prins Annulation3.1 Alkynyl Prins-Mediated Synthesis of Dienes for a [4+2] Cyclo- addition-Oxidation Sequence3.2 Alkynyl Prins Cyclization Adducts as Nazarov Cyclization Precursors3.3 Alkynyl Prins Cyclization in Natural Product Synthesis4 Alkynyl Aza-Prins Annulation4.1 Iminium Electrophiles4.2 Activated Iminium Electrophiles5 Alkynyl Aza-Prins Cyclizations in Natural Product Synthesis6 Summary and Outlook
- Published
- 2020
22. Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation
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Heng Wang, Zhenyang Lin, Yongjie Sun, Tilong Yang, Jialin Wen, and Xumu Zhang
- Subjects
inorganic chemicals ,Reaction mechanism ,010405 organic chemistry ,Chemistry ,Kinetics ,Oxocarbenium ,Enantioselective synthesis ,Ionic bonding ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Iridium ,Brønsted–Lowry acid–base theory - Abstract
Ionic hydrogenation has not been extensively explored, but is advantageous for challenging substrates such as unsaturated intermediates. Reported here is an iridium-catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans with high enantioselectivities. A variety of functionalities are compatible with this catalytic system. In the presence of a catalytic amount of the Brønsted acid HCl, an α-chloroether is generated in situ and subsequentially reduced. Kinetic studies suggest first-order kinetics in the substrate and half-order kinetics in the catalyst. A positive nonlinear effect, together with the half kinetic order, revealed a dimerization of the catalyst. Possible reaction pathways based on the monomeric iridium catalyst were proposed and DFT computational studies revealed an ionic hydrogenation pathway. Chloride abstraction and the cleavage of dihydrogen occur in the same step.
- Published
- 2020
23. Use of remote acyl groups for stereoselective 1,2-cis-glycosylation with fluorinated glucosazide thiodonors
- Author
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Martin Dračínský, Lucie Červenková Šťastná, Petra Cuřínová, Martin Kurfiřt, Vojtěch Hamala, and Jindřich Karban
- Subjects
Glycan ,Glycosylation ,biology ,Chemistry ,Stereochemistry ,Organic Chemistry ,Oxocarbenium ,Biochemistry ,Chemical synthesis ,carbohydrates (lipids) ,chemistry.chemical_compound ,biology.protein ,Moiety ,Stereoselectivity ,Physical and Theoretical Chemistry ,Protecting group ,Acyl group - Abstract
Fluorinated glycans are valuable probes for studying carbohydrate-protein interactions at the atomic level. Glucosamine is a ubiquitous component of glycans, and the stereoselective synthesis of α-linked fluorinated glucosamine is a challenge associated with the chemical synthesis of fluorinated glycans. We found that introducing a 6-O-acyl protecting group onto 3-fluoro and 4-fluoro glucosazide thiodonors endowed them with moderate α-selectivity in the glycosylation of carbohydrate acceptors, which was further improved by adjusting the acceptor reactivity via O-benzoylation. Excellent stereoselectivity was achieved for 3,6-di-O-acyl-4-fluoro analogues. The glycosylation of threonine-derived acceptors enabled the stereoselective synthesis of the protected fluorinated analogue of α-GlcNAc-O-Thr, a moiety abundant in cell-surface O-glycans of the protozoan parasite Trypanosoma cruzi. DFT calculations supported the involvement of transient cationic species which resulted from the stabilization of the oxocarbenium ion through O-6 acyl group participation.
- Published
- 2020
24. Catalytic enantioselective alkylation of 2-alkoxy-tetrahydrofurans
- Author
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Pang Jingxiang, Xuan Liu, Shaofa Sun, Zhushuang Bai, Gang Wang, and Lei Liu
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Carboxylic acid ,Organic Chemistry ,Enantioselective synthesis ,Oxocarbenium ,Alkylation ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Enantiopure drug ,chemistry ,Functional group ,Alkoxy group - Abstract
Catalytic asymmetric addition to non-resonance-stabilized oxocarbenium ions has remained a formidable challenge. Herein, we disclosed a nickel(II)-catalyzed asymmetric alkylation of non-resonance-stabilized, five-membered oxocarbenium ions generated in situ from 2-alkoxy tetrahydrofurans with a broad range of carboxylic acid derivatives. The reaction exhibits high efficiency, excellent enantioselectivity, and good functional group tolerance, and can be conducted on a large scale. Aside from five-membered oxocarbenium ions, six-membered and acyclic aliphatic species were also well tolerated with excellent enantiocontrol, thus providing a practical and robust method to access enantiopure α-alkyl substituted saturated ethers.
- Published
- 2020
25. How inverting β-1,4-galactosyltransferase-1 can quench a high charge of the by-product UDP3−in catalysis: a QM/MM study of enzymatic reaction with native and UDP-5′ thio galactose substrates
- Author
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Juraj Kóňa
- Subjects
Anomer ,Molecular model ,010405 organic chemistry ,Stereochemistry ,Chemistry ,Organic Chemistry ,Oxocarbenium ,Thio ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Acceptor ,0104 chemical sciences ,Catalysis ,QM/MM ,Molecular orbital ,Physical and Theoretical Chemistry - Abstract
The catalysis of inverting glycosyltransferases consists of several biophysical and biochemical processes during which the transfer of a sugar residue from the purine phosphate donor substrate to an acceptor substrate occurs with stereo-inversion of the anomeric C1 center at a product. During catalysis a highly charged phosphate by-product (UDP3−) is formed and a mechanism of how the enzyme stabilizes it back to the UDP2− form is not known. Using methods of molecular modeling (hybrid DFT-QM/MM calculations) we proposed and validated a catalytic mechanism of bovine inverting β-1,4-galactosyltransferase-1 (β4Gal-T1) with native (UDP-galactose) and thio donor substrates (UDP-5′ thio galactose). We focused on three aspects of the mechanism not yet investigated: (i) the formation of an oxocarbenium ion intermediate, which was only found for the retaining glycosyltransferases for the time being; (ii) the mechanism of stabilization of a highly charged phosphate by-product (UDP3−) back to its standard in vivo form (UDP2−); (iii) explanation for why in experimental measurements the rate of catalysis with the thio donor substrate is only 8% of the rate of that with the natural substrate. To understand the differences in the interaction patterns between the complexes enzyme : UDP-Gal and enzyme : UDP-5S-Gal, fragmented molecular orbital (FMO) decomposition energy analysis was carried out at the DFT level.
- Published
- 2020
26. Catalytic Cycle of Glycoside Hydrolase BglX from Pseudomonas aeruginosa and Its Implications for Biofilm Formation
- Author
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Julia Sanz-Aparicio, Mijoon Lee, Kiran V. Mahasenan, María T. Batuecas, Shahriar Mobashery, Choon Kim, Juan A. Hermoso, Jed F. Fisher, Neha Rana, Stefania De Benedetti, Dusan Hesek, University of Notre Dame, Ministerio de Ciencia, Innovación y Universidades (España), ALBA Synchrotron, and National Institutes of Health (US)
- Subjects
0301 basic medicine ,010405 organic chemistry ,Stereochemistry ,Pseudomonas aeruginosa ,Mutant ,Oxocarbenium ,Biofilm ,General Medicine ,Periplasmic space ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Catalytic cycle ,medicine ,Molecular Medicine ,Glycoside hydrolase ,Peptidoglycan - Abstract
8 pags., 5 figs., BglX is a heretofore uncharacterized periplasmic glycoside hydrolase (GH) of the human pathogen Pseudomonas aeruginosa. X-ray analysis identifies it as a protein homodimer. The two active sites of the homodimer comprise catalytic residues provided by each monomer. This arrangement is seen in, The work at the University of Notre Dame was supported by grants from the National Institutes of Health (GM61629 and GM131685), and that in Spain by a grant from MICIU Ministry (BFU2017-90030-P). The authors thank the staff from the ALBA (Barcelona, Spain) synchrotron facility for help in X-ray data collection and CRC of the University of Notre Dame for the computing resources. The authors acknowledge Grant P30 DK089507 from the National Institutes of Health for the BglX transposon mutant of P. aeruginosa.
- Published
- 2019
27. Highly Acidic Conjugate‐Base‐Stabilized Carboxylic Acids Catalyze Enantioselective oxa‐Pictet–Spengler Reactions with Ketals
- Author
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Helmi Ulrika Kirm, Chenfei Zhao, Märt Lõkov, Jaan Saame, Daniel Seidel, Minami Odagi, Khalil A. Abboud, Ivo Leito, and Zhengbo Zhu
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,Dihydropyran ,Carboxylic acid ,Enantioselective synthesis ,Oxocarbenium ,General Medicine ,Combinatorial chemistry ,Catalysis ,Stereocenter ,chemistry.chemical_compound ,chemistry ,Organocatalysis ,Carboxylate - Abstract
Acyclic ketone-derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone-derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well-known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion-binding to a thiourea site.
- Published
- 2019
28. Mechanistic Insight toward Understanding the Role of Charge in Thiourea Organocatalysis
- Author
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Travis Dudding, Rocío Durán, Matt Guest, Ivor Smajlagic, and Bárbara Herrera
- Subjects
010405 organic chemistry ,Chemistry ,Hydrogen bond ,Organic Chemistry ,Oxocarbenium ,Cationic polymerization ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Thiourea organocatalysis ,Thiourea ,Kinetic isotope effect ,Brønsted–Lowry acid–base theory - Abstract
Pyranylation and glycosylation are pivotal for accessing a myriad of natural products, pharmaceuticals, and drug candidates. Catalytic approaches for enabling these transformations are of utmost importance and integral to advancing this area of synthesis. In exploring this chemical space, a combined experimental and computational mechanistic study of pyranylation and 2-deoxygalactosylation catalyzed by a cationic thiourea organocatalyst is reported. To this end, a thiourea-cyclopropenium organocatalyst was employed as a model system in combination with an arsenal of mechanistic techniques, including 13C kinetic isotope effect experiments, deuterated labeling studies, variable-temperature 1H NMR spectroscopy, and density functional theory calculations. From these studies, two distinct reaction pathways were identified for this transformation corresponding to either dual hydrogen bond (H-bond) activation or Bronsted acid catalysis. The former involving thiourea orchestrated bifurcated hydrogen bonding proceeded in an asynchronous concerted fashion. In contrast, the latter stepwise mechanism involving Bronsted acid catalysis hinged upon the formation of an oxocarbenium intermediate accompanied by subsequent alcohol addition.
- Published
- 2019
29. Open-Close Strategy toward the Organocatalytic Generation of 2-Deoxyribosyl Oxocarbenium Ions: Pyrrolidine-Salt-Catalyzed Synthesis of 2-Deoxyribofuranosides
- Author
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Pavan K. Kancharla, Titli Ghosh, and Ananya Mukherji
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,Glycosylation ,chemistry ,Organic Chemistry ,Polymer chemistry ,Oxocarbenium ,Salt (chemistry) ,Physical and Theoretical Chemistry ,Counterion ,Pyrrolidine ,Ion ,Catalysis - Published
- 2019
30. Unusual Transformations of Strain-Heightened Oxetanes
- Author
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Amy R. Howell, Louis P. Riel, and Jason An
- Subjects
chemistry.chemical_classification ,Models, Molecular ,Molecular Structure ,Cyclopropanation ,Oxocarbenium ,Substituent ,Stereoisomerism ,General Medicine ,General Chemistry ,Oxetane ,Combinatorial chemistry ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Ethers, Cyclic ,Enol ether ,Organic synthesis ,Dimethyldioxirane - Abstract
Oxetanes are important motifs for drug discovery and are valuable templates in organic synthesis. Much of their use as synthetic intermediates exploits their inherent strain, often resulting in chain extensions at the expense of the heterocycle. Modifications on the carbon alpha to the oxygen of oxetanes, such as the C═O of β-lactones, extend the modes of reactivity. Nevertheless, the outcomes are still largely predictable. On the other hand, other alpha modifications, such as a ═CH2, a spiro-oxiranyl moiety, or a spiro-cyclopropyl group, increase strain and open pathways not available to simple oxetanes or β-lactones. Methods in generating 2-methyleneoxetanes, 1,5-dioxaspiro[3.2]hexanes, and 4-oxaspiro[2.3]hexanes have been developed by us and others. To date, reactions of these systems have sometimes been predictable, but often the outcomes have been unexpected. This has provided fertile ground for thinking about what controls reactivity and what other reaction pathways might be accessible to these strain-heightened oxetanes.This Account summarizes the published literature on the most straightforward approaches to 2-methyleneoxetanes, dioxaspirohexanes, and oxaspirohexanes and on their reactivity. In contrast to simple oxetanes, reactions of 2-methyleneoxetanes with nucleophiles at C4 release an enolate rather than an alkoxide. Also, 2-methyleneoxetanes can be converted to homopropargyl alcohols or undergo a silicon accelerated isomerization/electrocyclic ring opening, processes accessible only because of the exocyclic double bond. In addition, oxetane oxocarbenium ions, derived from protonation of the enol ether, can react with nucleophiles to provide 2,2-disubstituted oxetanes. Oxaspirohexanes are readily prepared by Simmons-Smith cyclopropanation of 2-methyleneoxetanes. These unusual systems undergo a variety of substituent dependent rearrangements in the presence of the Lewis acid BF3·Et2O. In addition, upon treatment with Zeise's dimer, oxaspirohexanes are transformed to synthetically useful 3-methylenetetrahydrofurans. Dioxaspirohexanes are easily accessed by dimethyldioxirane oxidation of 2-methyleneoxetanes. Predictably, dioxaspirohexanes react with many nucleophiles to give α-functionalized-β'-hydroxy ketones. Unexpectedly, 2,2-disubstituted oxetanes can also be selectively produced. This latter pathway has led to further unusual transformations, illuminating computational studies, and novel routes to biologically relevant molecules.
- Published
- 2021
31. Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase
- Author
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Asuka Shirakawa, Kumpei Yano, Seiji Masui, Koichi Fukase, Antonio Molinaro, Yoshiyuki Manabe, Roberta Marchetti, Alba Silipo, Shirakawa, A., Manabe, Y., Marchetti, R., Yano, K., Masui, S., Silipo, A., Molinaro, A., and Fukase, K.
- Subjects
Steric effects ,Glycan ,Glycosylation ,Stereochemistry ,Oxocarbenium ,Mannose ,Neuraminidase ,Chemical synthesis ,Catalysis ,Mass Spectrometry ,chemistry.chemical_compound ,Sialic Acid ,Influenza A Virus, H1N1 Subtype ,Polysaccharides ,deuterium labeling ,Polysaccharide ,biology ,General Chemistry ,Deuterium ,Sialic acid ,carbohydrates (lipids) ,chemistry ,N-glycan ,biology.protein ,Sialic Acids ,Spectrophotometry, Ultraviolet - Abstract
The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds. Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate. Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation. Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy. The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition. The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch. Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
- Published
- 2021
32. Side Chain Conformation Restriction in the Catalysis of Glycosidic Bond Formation by Leloir Glycosyltransferases, Glycoside Phosphorylases, and Transglycosidases
- Author
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David Crich and Jonathan C. K. Quirke
- Subjects
chemistry.chemical_classification ,Anomer ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Oxocarbenium ,Glycoside ,Glycosidic bond ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,Article ,0104 chemical sciences ,chemistry.chemical_compound ,Glycosyltransferase ,Side chain ,biology.protein ,Glycoside hydrolase ,Glycosyl - Abstract
Carbohydrate side chain conformation is an important factor in the control of reactivity at the anomeric center, ie, in the making and breaking of glycosidic bonds, whether chemically or, for hydrolysis, by glycoside hydrolases. In nature glycosidic bond formation is catalyzed out by glycosyltransferases (GTs), glycoside phosphoryases, and transglycosidases. By analysis of 118 crystal structures of sugar nucleotide dependent (Leloir) GTs, 136 crystal structures of glycoside phosphorylases, and 54 crystal structures of transglycosidases bound to hexopyranosides or their analogs at the donor site (-1 site), we determined that most enzymes that catalyze glycoside synthesis, be they GTs, glycoside phosphorylases or transglycosidases, restrict their substrate side chains to the most reactive gauche,gauche (gg) conformation to achieve maximum stabilization of the oxocarbenium ion-like transition state for glycosyl transfer. The galactose series deviates from this trend, with α-galactosyltransferases preferentially restricting their substrates to the second-most reactive gauche,trans (gt) conformation, and β-galactosyltransferases favoring the least reactive trans,gauche (tg) conformation. This insight will help progress the design and development of improved, conformationally-restricted GT inhibitors that take advantage of these inherent side chain preferences.
- Published
- 2021
33. Synthesis of furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free radical.
- Author
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Worawalai, Wisuttaya, Khongchai, Phonpimon, Surachaitanawat, Nantaporn, and Phuwapraisirisan, Preecha
- Abstract
Furofuran lignans such as sesamin have been recognized as promising antidiabetic agents as they possess curative as well as preventive effects toward diabetes complications. However, to date the structure-activity relationship has not been investigated due to the lack of a practical synthetic route capable of producing diverse furofuran lignans. Herein, we first introduced a single-step synthesis of these compounds starting from samin ( 4). Reaction of samin with a variety of electron-rich phenolics under acidic conditions afforded a total of 23 diverse furofuran lignans. On examination their inhibitions against α-glucosidase and free radicals, lignans having a free hydroxy group showed considerably enhanced inhibition, compared with their corresponding starter 4 and related lignans sesamin ( 1) and sesamolin ( 3). In addition, the mechanism underlying the α-glucosidase inhibition of a particular active lignan ( epi -6) was verified to be mixed manner between competitive and noncompetitive inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
34. Brønsted Acid-Catalyzed Direct Substitution of 2-Ethoxytetrahydrofuran with Trifluoroborate Salts.
- Author
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Fisher, Kayla M. and Bolshan, Yuri
- Subjects
- *
BRONSTED acids , *LEWIS acidity , *TETRAHYDROFURAN - Abstract
Metal-free transformations of organotrifluoroborates are advantageous since they avoid the use of frequently expensive and sensitive transition metals. Lewis acid-catalyzed reactions involving potassium trifluoroborate salts have emerged as an alternative to metal-catalyzed protocols. However, the drawbacks to these methods are that they rely on the generation of unstable boron dihalide species, thereby resulting in low functional group tolerance. Recently, we discovered that in the presence of a Brønsted acid, trifluoroborate salts react rapidly with in situ generated oxocarbenium ions. Here, we report Brønsted acid-catalyzed direct substitution of 2-ethoxytetrahydrofuran using potassium trifluoroborate salts. The reaction occurs when tetrafluoroboric acid is used as a catalyst to afford functionalized furans in moderate to excellent yields. A variety of alkenyl- and alkynyltrifluoroborate salts readily participate in this transformation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
35. Vinylsilane-mediated synthesis of styryl-lactone frameworks.
- Author
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Fearnley, Stephen Philip and Lory, Pedro
- Subjects
- *
VINYLSILANES , *LACTONES , *ORGANIC synthesis , *STYRYL compounds , *ENOL ethers , *STEREOSELECTIVE reactions , *ETHERIFICATION - Abstract
A general route to several styryl-lactone frameworks is presented. Starting from a known enol ether, stereoselective epoxidation and methanolysis yields a series of three distinct hydroxyacetals, each further functionalized by etherification with an allylic vinylsilane fragment. A highly efficient Lewis acid-promoted intramolecular annulation at the tethered oxocarbenium allows direct entry to cis -fused bicyclic ether cores. Further manipulation delivers a variety of additional styryl-lactone motifs and analogs; for example, simple allylic oxidation yields 3-deoxyisoaltholactone, in just five steps overall. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
36. The inverting mechanism of the metal ion-independent LanGT2: the first step to understand the glycosylation of natural product antibiotic precursors through QM/MM simulations
- Author
-
Gonzalo A. Jaña and Fernanda Mendoza
- Subjects
chemistry.chemical_classification ,Biological Products ,Glycosylation ,Stereochemistry ,Organic Chemistry ,Oxocarbenium ,Leaving group ,Landomycin ,Biochemistry ,Amino acid ,QM/MM ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Moiety ,Physical and Theoretical Chemistry - Abstract
Glycosyltransferases (GTs) from the GT1 family are responsible for the glycosylation of various important organic structures such as terpenes, steroids and peptide antibiotics, making it one of the most intensely studied families of GTs. The target of our study, LanGT2, is a member of the GT1 family that uses an inverting mechanism for transferring olivose from TDP-olivose, the donor substrate, to the natural product tetrangulol (Tet), the precursor of the antibiotic landomycin A. X-ray crystallography in conjunction with mutagenesis experiments has revealed the catalytic significance of 3 amino acids (Ser10, Ser219 and Asp137), suggesting Asp137 as the base catalyst. In the absence of X-ray structures that include the acceptor substrate Tet, in silico experiments and MD simulations that have modeled ternary complexes propose that Asp137 could recruit a water molecule to facilitate the nucleophilic activation of Tet, since the distance between Asp137 and the nucleophile is too long to directly deprotonate the nucleophilic moiety. So far, there is no computational evidence regarding the precise mechanism by which LanGT2 catalyzes the transfer of olivose, which raises questions such as: is a water-assisted mechanism possible? and how does this metal ion-independent GT stabilize the growing negative charge of the diphosphate leaving group? In this work, the QM/MM approach was used to unravel the catalytic mechanism of LanGT2, and to identify the role of crucial catalytic amino acids at a molecular level. Our calculations show that the minimum energy path (MEP) describes an SN2-like mechanism, identifying an oxocarbenium ion-like TS in which the olivosyl moiety adopts a 4H3 conformation. Interactions established between the diphosphate group of TDP and Ser10, Ser219, Arg220 and His283 are key to stabilize the development of charge on the leaving group. Our work also suggests that a water-mediated proton transfer mechanism is feasible, in which the water molecule is key to stabilize the phenolate ion-like nucleophile in the TS. This is the first computational insight into the inverting mechanism of an antibiotic natural product GT, and its implications may serve to guide the design of new biocatalysts for natural product glycodiversification.
- Published
- 2021
37. Mechanism and origins of selectivity in the enantioselective oxa-Pictet-Spengler reaction: a cooperative catalytic complex from a hydrogen bond donor and chiral phosphoric acid
- Author
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Mark A. Maskeri, Karl A. Scheidt, Daniel M. Walden, Taisiia Feoktistova, Matthew J. O'Connor, Alexander C. Brueckner, and Paul Ha-Yeon Cheong
- Subjects
inorganic chemicals ,Pictet–Spengler reaction ,Hydrogen bond ,Catalytic complex ,organic chemicals ,Oxocarbenium ,Enantioselective synthesis ,Substrate (chemistry) ,General Chemistry ,Combinatorial chemistry ,Catalysis ,chemistry.chemical_compound ,Chemistry ,chemistry ,Phosphoric acid - Abstract
Enantioselective additions to oxocarbenium ions are high-value synthetic transformations but have proven challenging to achieve. In particular, the oxa-Pictet–Spengler reaction has only recently been rendered enantioselective. We report experimental and computational studies on the mechanism of this unusual transformation. Herein we reveal that this reaction is hypothesized to proceed through a self-assembled ternary hydrogen bonding complex involving the substrate, chiral phosphate ion, and a urea hydrogen-bond donor. The computed transition state reveals C2-symmetric grooves in the chiral phosphate that are occupied by the urea and substrate. Occupation of one of these grooves by the urea co-catalyst tunes the available reactive volume and enhances the stereoselectivity of the chiral phosphate catalyst., A new model for the cooperative catalytic oxa-Pictet–Spengler reaction is disclosed. Supporting spectroscopic, kinetic, and computational quantum mechanics studies permit the rationalization of the reaction's observed enantioselectivity.
- Published
- 2021
38. Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
- Author
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Yves Blériot, Ana Ardá, Antonio Franconetti, Jesús Jiménez-Barbero, Sébastien Thibaudeau, and Juan Luis Asensio
- Subjects
Models, Molecular ,Glycosylation ,oxocarbenium ion ,Molecular Conformation ,Oxocarbenium ,Ionic bonding ,Context (language use) ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Nucleophile ,Computational chemistry ,glycosylation reaction ,Molecule ,Reactivity (chemistry) ,Glycosyl ,Ions ,010405 organic chemistry ,oxocarbenium cations ,glycosyl cations ,General Medicine ,General Chemistry ,0104 chemical sciences ,glycosyl ions ,chemistry ,contact ion pairs ,Methane ,counterions and donors - Abstract
Carbohydrates (glycans, saccharides, and sugars) are essential molecules in all domains of life. Research on glycoscience spans from chemistry to biomedicine, including material science and biotechnology. Access to pure and well-defined complex glycans using synthetic methods depends on the success of the employed glycosylation reaction. In most cases, the mechanism of the glycosylation reaction is believed to involve the oxocarbenium ion. Understanding the structure, conformation, reactivity, and interactions of this glycosyl cation is essential to predict the outcome of the reaction. In this Account, building on our contributions on this topic, we discuss the theoretical and experimental approaches that have been employed to decipher the key features of glycosyl cations, from their structures to their interactions and reactivity. We also highlight that, from a chemical perspective, the glycosylation reaction can be described as a continuum, from unimolecular SN1 with naked oxocarbenium cations as intermediates to bimolecular SN2-type mechanisms, which involve the key role of counterions and donors. All these factors should be considered and are discussed herein. The importance of dissociative mechanisms (involving contact ion pairs, solvent-separated ion pairs, solvent-equilibrated ion pairs) with bimolecular features in most reactions is also highlighted. The role of theoretical calculations to predict the conformation, dynamics, and reactivity of the oxocarbenium ion is also discussed, highlighting the advances in this field that now allow access to the conformational preferences of a variety of oxocarbenium ions and their reactivities under SN1-like conditions. Specifically, the ground-breaking use of superacids to generate these cations is emphasized, since it has permitted characterization of the structure and conformation of a variety of glycosyl oxocarbenium ions in superacid solution by NMR spectroscopy. We also pay special attention to the reactivity of these glycosyl ions, which depends on the conditions, including the counterions, the possible intra- or intermolecular participation of functional groups that may stabilize the cation and the chemical nature of the acceptor, either weak or strong nucleophile. We discuss recent investigations from different experimental perspectives, which identified the involved ionic intermediates, estimating their lifetimes and reactivities and studying their interactions with other molecules. In this context, we also emphasize the relationship between the chemical methods that can be employed to modulate the sensitivity of glycosyl cations and the way in which glycosyl modifying enzymes (glycosyl hydrolases and transferases) build and cleave glycosidic linkages in nature. This comparison provides inspiration on the use of molecules that regulate the stability and reactivity of glycosyl cations.
- Published
- 2021
39. Development of mCherry tagged UdgX as a highly sensitive molecular probe for specific detection of uracils in DNA
- Author
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Shashanka Aroli, Kapudeep Karmakar, Dipshikha Chakravortty, Umesh Varshney, Somnath Dutta, and Madhurima Datta
- Subjects
0301 basic medicine ,Recombinant Fusion Proteins ,Mycobacterium smegmatis ,Biophysics ,Oxocarbenium ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bacterial Proteins ,Uracil ,Molecular Biology ,Gene ,biology ,DNA ,Cell Biology ,biology.organism_classification ,Luminescent Proteins ,030104 developmental biology ,chemistry ,Deoxyribose ,Molecular Probes ,030220 oncology & carcinogenesis ,Molecular probe ,mCherry ,Genome, Bacterial - Abstract
Uracil is not always a mistakenly occurring base in DNA. Uracils in DNA genomes are known to be important in the life cycles of Bacillus subtilis phages (PBS1/2) and the malarial parasite, Plasmodium falciparum; and have been implicated in the development of fruit fly and antibody maturation in B-lymphocytes. Availability of a sensitive, specific and robust technique for the detection uracils in genes/genomes is essential to understand its varied biological roles. Mycobacterium smegmatis UdgX (MsmUdgX), identified and characterised in our laboratory, forms covalent complexes with the uracil sites in DNA in a specific manner. MsmUdgX cleaves the glycosidic bond between uracil and the deoxyribose sugar in DNA to produce uracilate and oxocarbenium ions. The oxocarbenium ion is then captured into a covalent complex by the nucleophilic attack of a histidine side chain of MsmUdgX. Here, we describe the use of a fusion protein, mCherry tagged MsmUdgX (mChUdgX), which combines the property of MsmUdgX to covalently and specifically bind the uracil sites in the genome, with the sensitivity of fluorescent detection of mCherry as a reporter. We show that both the purified mChUdgX and the Escherichia coli cell-extracts overexpressing mChUdgX provide high sensitivity and specificity of detecting uracils in DNA.
- Published
- 2019
40. Insights into the Stability of Siloxy Carbene Intermediates and Their Corresponding Oxocarbenium Ions
- Author
-
Daniel L. Priebbenow
- Subjects
Silanes ,010405 organic chemistry ,Cyclopropanation ,Organic Chemistry ,Reactive intermediate ,Oxocarbenium ,010402 general chemistry ,01 natural sciences ,Chemical reaction ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Singlet state ,Triplet state ,Carbene - Abstract
Siloxy carbenes, formed thermally or photochemically from acyl silanes via a 1,2-Brook rearrangement, are intriguing reactive intermediates that partake in a range of chemical reactions. To gain further insight into the properties of this class of carbenes, the thermodynamic stabilities of a series of known siloxy carbenes were explored on the basis of hydrogenation enthalpies. Calculations were conducted at the B3LYP-D3(BJ) level (using dispersion-corrected DFT) on siloxy carbenes (X-C-OSiR3, singlet and triplet state), oxocarbenium ions (X-CH-OSiR3+), and their hydrogen addition products (X-CH2-OSiR3). Overall, strong correlation between singlet-triplet gaps and hydrogenation enthalpies was observed. Carbene stabilization enthalpy (CSE) values were also determined to provide additional insight into the structural features that influence the stability of siloxy carbenes.
- Published
- 2019
41. Structural and Computational Analysis of 2‐Halogeno‐Glycosyl Cations in the Presence of a Superacid: An Expansive Platform
- Author
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Yves Blériot, Agnès Mingot, Nuria Aiguabella font, Ryan Gilmour, Amélie Martin, Sébastien Thibaudeau, Ana Ardá, Jesús Jiménez-Barbero, Marialuisa Aufiero, Jérôme Désiré, and Ludivine Lebedel
- Subjects
010405 organic chemistry ,Oxocarbenium ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry.chemical_compound ,Nucleophile ,chemistry ,Computational chemistry ,Intramolecular force ,Electrophile ,Reactivity (chemistry) ,Glycosyl ,Superacid ,Computational analysis ,Deoxygenation - Abstract
An expansive NMR-based structural analysis of elusive glycosyl cations derived from natural and non-natural monosaccharides in superacids is disclosed. For the first time, it has been possible to explore the consequence of deoxygenation and halogen substitution at the C2 position in a series of 2-halogenoglucosyl, galactosyl, and mannosyl donors in the condensed phase. These cationic intermediates were characterized using low-temperature in situ NMR experiments supported by DFT calculations. The 2-bromo derivatives display intramolecular stabilization of the glycosyl cations. Introducing a strongly electron-withdrawing fluorine atom at C2 exerts considerable influence on the oxocarbenium ion reactivity. In a superacid, these oxocarbenium ions are quenched by weakly coordinating SbF6 - anions, thereby demonstrating their highly electrophilic character and their propensity to interact with poor nucleophiles.
- Published
- 2019
42. Palladium-catalysed C−H glycosylation for synthesis of C-aryl glycosides
- Author
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Wanjun Zhu, Gong Chen, Zhiqiang Deng, Zeyi Huang, Shuang An, Gang He, and Quanquan Wang
- Subjects
Glycosylation ,Process Chemistry and Technology ,Aryl ,Oxocarbenium ,chemistry.chemical_element ,Bioengineering ,Biochemistry ,Combinatorial chemistry ,Chemical synthesis ,Catalysis ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Glycosyl ,Palladium - Abstract
C-aryl glycosides are widely found in nature and play important roles in drug design. Despite the significant progress made over the past few decades, efficient and stereoselective synthesis of complex C-aryl glycosides remains challenging, lagging far behind the state of the art of the synthesis of O- or N-glycosides. Here, we report a simple and powerful bioinspired strategy for the stereoselective synthesis of C-aryl glycosides via palladium-catalysed ortho-directed C(sp2)−H functionalization of arenes and heteroarenes with easily accessible glycosyl chloride donors. The catalytic palladacycle intermediate generated via C−H palladation provides a soft aryl nucleophile that can react with glycosyl oxocarbenium ion partners with high efficiency and excellent stereocontrol. The method can be applied to a wide range of arene and heteroarene substrates, glycosyl chloride donors and auxiliary groups. It can simplify the synthesis of a variety of complex C-aryl glycosides and offers a tool for late-stage modification of drug molecules. C-aryl glycosides are present in many natural products and of interest in drug design, but their chemical synthesis is challenging. This work reports an efficient and diastereoselective ortho-directed C−H glycosylation of arenes and heteroarenes with glycosyl chloride using a palladium catalyst.
- Published
- 2019
43. Constrained sialic acid donors enable selective synthesis of α-glycosides
- Author
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Keiichi Kato, Taro Udagawa, Sachi Asano, Naoko Komura, Hidenori Tanaka, Hideharu Ishida, Makoto Kiso, Akihiro Imamura, and Hiromune Ando
- Subjects
chemistry.chemical_classification ,Glycan ,Multidisciplinary ,Anomer ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Chemical structure ,Oxocarbenium ,Glycoside ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Sialic acid ,chemistry.chemical_compound ,Residue (chemistry) ,biology.protein ,Stereoselectivity - Abstract
Sweet spot for making oligosaccharides Sugars pose a challenge for chemists: how to string together functional group–rich building blocks that can adopt multiple conformations. Two papers in this issue used sugar building blocks constrained by a macrocyclic linker to encourage formation of a specific glycosidic linkage (see the Perspective by Pohl). Ikuta et al. used glucose building blocks containing a linker that changes the sugar conformation to synthesize cyclic oligomers with only three or four units. The linker changes the conformation of the glucose monomers, enabling them to come together despite the strain in the final structure. Komura et al. prepared sialic acid building blocks with a linker that allows for selective formation of the α-anomeric linkage with a range of nucleophiles. They synthesized dimers of sialic acid with many different linkages and a pentamer with four α(2,8) linkages. This method enabled chemical synthesis of components of mammalian glycans involved in brain development, cell adhesion, and immune response. Science , this issue p. 674 , p. 677 ; see also p. 631
- Published
- 2019
44. Effects of chloride ions in acid-catalyzed biomass dehydration reactions in polar aprotic solvents
- Author
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Robert L. Johnson, Matthew Neurock, Theodore W. Walker, William A. Elliott, James A. Dumesic, Brent H. Shanks, Peng Bai, Benginur Demir, Chotitath Sanpitakseree, Max A. Mellmer, Kaiwen Ma, and Robert M. Rioux
- Subjects
0301 basic medicine ,Science ,Inorganic chemistry ,Oxocarbenium ,General Physics and Astronomy ,02 engineering and technology ,Chloride ,Article ,General Biochemistry, Genetics and Molecular Biology ,Catalysis ,Chemical kinetics ,03 medical and health sciences ,chemistry.chemical_compound ,Deprotonation ,medicine ,Reactivity (chemistry) ,lcsh:Science ,Multidisciplinary ,Solvation ,General Chemistry ,021001 nanoscience & nanotechnology ,030104 developmental biology ,chemistry ,lcsh:Q ,0210 nano-technology ,Hydroxymethylfurfural ,medicine.drug - Abstract
The use of polar aprotic solvents in acid-catalyzed biomass conversion reactions can lead to improved reaction rates and selectivities. We show that further increases in catalyst performance in polar aprotic solvents can be achieved through the addition of inorganic salts, specifically chlorides. Reaction kinetics studies of the Brønsted acid-catalyzed dehydration of fructose to hydroxymethylfurfural (HMF) show that the use of catalytic concentrations of chloride salts leads to a 10-fold increase in reactivity. Furthermore, increased HMF yields can be achieved using polar aprotic solvents mixed with chlorides. Ab initio molecular dynamics simulations (AIMD) show that highly localized negative charge on Cl− allows the chloride anion to more readily approach and stabilize the oxocarbenium ion that forms and the deprotonation transition state. High concentrations of polar aprotic solvents form local hydrophilic environments near the reactive hydroxyl group which stabilize both the proton and chloride anions and promote the dehydration of fructose., Despite the potential advantages of using polar aprotic solvents for biomass upgrading reactions, fundamental understanding of these solvation effects is limited at present. Here, the authors show that further increases in catalyst performance in polar aprotic solvents can be achieved through the addition of inorganic salts.
- Published
- 2019
45. 1,2-trans Glycosylation via Neighboring Group Participation of 2-O-Alkoxymethyl Groups: Application to One-Pot Oligosaccharide Synthesis
- Author
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Milandip Karak, Kohei Torikai, Masahiko Suenaga, Yohei Joh, and Tohru Oishi
- Subjects
chemistry.chemical_classification ,Glycosylation ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Oxocarbenium ,Substituent ,Glycosidic bond ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Intramolecular force ,Reactivity (chemistry) ,Stereoselectivity ,Physical and Theoretical Chemistry ,Selectivity - Abstract
The use of 2- O-alkoxymethyl groups as effective stereodirecting substituents for the construction of 1,2- trans glycosidic linkages is reported. The observed stereoselectivity arises from the intramolecular formation of a five-membered cyclic architecture between the 2- O-alkoxymethyl substituent and the oxocarbenium ion, which provides the expected facial selectivity. Furthermore, the observed stereocontrol and the extremely high reactivity of 2- O-alkoxymethyl-protected donors allowed development of a one-pot sequential glycosylation strategy that should become a powerful tool for the assembly of oligosaccharides.
- Published
- 2019
46. Reaction mechanism of nucleoside 2′-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate
- Author
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Jesús Fernández-Lucas, Leticia González, Pedro A. Sánchez-Murcia, Federico Gago, Jon Del Arco, Almudena Perona, Ministerio de Economía y Competitividad (España), Fundación Banco Santander, and University of Vienna
- Subjects
0301 basic medicine ,Reaction mechanism ,Protein Conformation ,Stereochemistry ,Oxocarbenium ,Reaction intermediate ,Molecular Dynamics Simulation ,Proof of Concept Study ,01 natural sciences ,Biochemistry ,Catalysis ,03 medical and health sciences ,SN1 reaction ,Catalytic Domain ,Lactobacillus leichmannii ,0103 physical sciences ,Pentosyltransferases ,Physical and Theoretical Chemistry ,Bond cleavage ,Biología molecular ,010304 chemical physics ,biology ,Chemistry ,Organic Chemistry ,Química orgánica ,Active site ,Substrate (chemistry) ,Kinetics ,030104 developmental biology ,Models, Chemical ,biology.protein ,Quantum Theory ,Thermodynamics - Abstract
Insight into the catalytic mechanism of Lactobacillus leichmannii nucleoside 2′-deoxyribosyltransferase (LlNDT) has been gained by calculating a quantum mechanics-molecular mechanics (QM/MM) free-energy landscape of the reaction within the enzyme active site. Our results support an oxocarbenium species as the reaction intermediate and thus an S1 reaction mechanism in this family of bacterial enzymes. Our mechanistic proposal is validated by comparing experimental kinetic data on the impact of the single amino acid replacements Tyr7, Glu98 and Met125 with Ala, Asp and Ala/norLeu, respectively, and accounts for the specificity shown by this enzyme on a non-natural substrate. This work broadens our understanding of enzymatic C-N bond cleavage and C-N bond formation., Financial support from the FWF (Lise Meitner Program M 2260) to PAS-M, the Spanish Ministerio de Economía y Competitividad (SAF2015-64629-C2-2-R) to F. G. and Grants XSAN001906 from the Santander Foundation to J. F. L. is gratefully acknowledged. We thank the University of Vienna for computational resources at the Institute of Theoretical Chemistry.
- Published
- 2019
47. Asymmetric construction of polycyclic indole derivatives with different ring connectivities by an organocatalysis triggered two-step sequence
- Author
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Yan-Kai Liu, Chao-Chao Xie, and Rui Tan
- Subjects
Indole test ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Oxocarbenium ,Alkylation ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,0104 chemical sciences ,Organocatalysis ,Intramolecular force ,Moiety ,Stereoselectivity - Abstract
An organocatalysis triggered highly regio- and stereoselective two-step sequence between hemiacetals and indole-containing nitroolefins was developed. The key to the success of this sequence was the intramolecular oxocarbenium ion induced collective alkylation at the C3, C2, or N1-position of the indole moiety, respectively, providing biologically important polycyclic indole derivatives with different ring connectivities. An unexpected epimerization was observed during the C3-alkylation process, which generated products with different relative configurations compared with the C2- and N1-alkylation products.
- Published
- 2019
48. Total Synthesis of the fungal metabolite Trienylfuranol A via Nucleophilic Diastereodivergent Additions to Oxocarbenium Ions
- Author
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Jamal Ouazzani, Pascal Retailleau, Guillaume Arcile, Jean-François Betzer, Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
- Subjects
010405 organic chemistry ,Chemistry ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Organic Chemistry ,Oxocarbenium ,Total synthesis ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,0104 chemical sciences ,3. Good health ,Ion ,Fungal metabolite ,Nucleophile ,Physical and Theoretical Chemistry - Abstract
International audience; Herein, we describe the first total synthesis of trienylfuranol A, a fungal triene-substituted tetrahydrofuran metabolite. The stereoselectivity of the chiral center bearing the trienyl side chain was diastereodivergently controlled by the addition of nucleophilic species on substituted gamma-butyrolactone. Remarkably, the C-nucleophilic species or hydride addition onto oxocarbenium intermediate leads to the opposite diastereoselectivity reported for Kishi or Woerpel models. The use of Hantzsch ester (HEH) as organic hydride donor has enabled us to access to the desired stereochemistry. The total synthesis of trienylfuranol A was achieved in 8 steps from acetaldehyde and pyruvic acid.
- Published
- 2021
49. A Platform for Alkene Carbofunctionalization with Diverse Nucleophiles
- Author
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Travis L. Buchanan, Ya-Nong Wang, Kami L. Hull, Alexander M. Veatch, and Samuel N. Gockel
- Subjects
chemistry.chemical_classification ,chemistry ,Nucleophile ,Alkene ,Intermolecular force ,Electrophile ,Oxocarbenium ,chemistry.chemical_element ,Carbon ,Combinatorial chemistry - Abstract
A general system achieving three-component intermolecular carbofunctionalization of alkenes is presented. A range of substituted alkenes are functionalized with α-bromo carbonyl electrophiles and nitrogen, oxygen, and carbon nucleophiles. Mechanistic findings support the intermediacy of a cyclic oxocarbenium ion.
- Published
- 2021
50. Nitrogen-Centered Radical-Mediated Cascade Amidoglycosylation of Glycals
- Author
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Chunyu Zhu, Zhiqiang Pan, Yuzhen Ding, Fengyuan Peng, Wenbin Shang, and Chengfeng Xia
- Subjects
chemistry.chemical_classification ,Anomer ,Glycosylation ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Nitrogen ,Organic Chemistry ,Oxocarbenium ,Selective catalytic reduction ,Glycosidic bond ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Cascade ,Molecule ,Glycosides ,Physical and Theoretical Chemistry ,Oxidation-Reduction - Abstract
A nitrogen-centered radical-mediated strategy for preparing 1,2-trans-2-amino-2-deoxyglycosides in one step was established. The cascade amidoglycosylation was initiated by a benzenesulfonimide radical generated from NFSI under the catalytic reduction of TEMPO. The benzenesulfonimide radical was electrophilically added to the glycals, and then the resulting glycosidic radical was converted to oxocarbenium upon oxidation by TEMPO+, which enabled the following anomeric specific glycosylation.
- Published
- 2021
Catalog
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