-
Angewandte Chemie (International Ed. in... Feb 2021By using Rh-H catalysis, we couple α-nitroesters and alkynes to prepare α-amino-acid precursors. This atom-economical strategy generates two contiguous stereocenters,...
By using Rh-H catalysis, we couple α-nitroesters and alkynes to prepare α-amino-acid precursors. This atom-economical strategy generates two contiguous stereocenters, with high enantio- and diastereocontrol. In this transformation, the alkyne undergoes isomerization to generate a Rh -π-allyl electrophile, which is trapped by an α-nitroester nucleophile. A subsequent reduction with In powder transforms the allylic α-nitroesters to the corresponding α,α-disubstituted α-amino esters.
Topics: Alkynes; Amino Acids; Catalysis; Coordination Complexes; Esters; Hydrogen; Rhodium; Stereoisomerism
PubMed: 33411337
DOI: 10.1002/anie.202014015 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2022The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly... (Review)
Review
The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.
Topics: Alkadienes; Alkynes; Catalysis; Cyclization; Indicators and Reagents; Nickel; Rhodium
PubMed: 34986277
DOI: 10.1002/chem.202104230 -
Chemical Record (New York, N.Y.) May 2022Azide-modified nucleosides are important building blocks for RNA and DNA functionalization by click chemistry based on azide-alkyne cycloaddition. This has put demand on... (Review)
Review
Azide-modified nucleosides are important building blocks for RNA and DNA functionalization by click chemistry based on azide-alkyne cycloaddition. This has put demand on synthetic chemistry to develop approaches for the preparation of azide-modified nucleoside derivatives. We review here the available methods for the synthesis of various nucleosides decorated with azido groups at the sugar residue or nucleobase, their incorporation into oligonucleotides and cellular RNAs, and their application in azide-alkyne cycloadditions for labelling and functionalization.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Nucleosides; RNA
PubMed: 35189013
DOI: 10.1002/tcr.202100322 -
Bioconjugate Chemistry Apr 2020Bioorthogonal chemistry has mainly been developed for proteins and carbohydrates. The chemistry of nucleic acids is different, and bioorthogonal labeling strategies that... (Review)
Review
Bioorthogonal chemistry has mainly been developed for proteins and carbohydrates. The chemistry of nucleic acids is different, and bioorthogonal labeling strategies that were successfully applied for proteins and carbohydrates cannot be simply transferred to DNA and RNA. Cycloadditions play a central role for bioorthogonal chemistry with nucleic acids. postsynthetic labeling of DNA and RNA requires copper-free variants of cycloaddition chemistry to achieve "bio"orthogonality that can be applied even in living cells. Currently, there are three major types of copper-free cycloadditions available for nucleic acids: (i) the ring-strain-promoted azide-alkyne cycloadditions, (ii) the "photoclick" 1,3-dipolar cycloadditions, and (iii) the Diels-Alder reactions with inverse electron demand. In principle, bioorthogonally reactive building blocks for postsynthetic modifications of nucleic acids by cycloaddition can be prepared by three different ways: (i) The organic synthesis of DNA and RNA applies phosphoramidites as building blocks for solid-phase automated chemistry. (ii) The biochemical preparation of DNA and RNA by primer extension (PEX) and PCR applies triphosphates as building blocks together with DNA/RNA polymerases, and works in aqueous buffer. (iii) DNA and RNA is labeled by the intrinsic metabolism in cells using bioorthogonally reactive nucleosides. In contrast to proteins and carbohydrates, for which metabolic labeling strategies are well developed, there are only a few examples in the literature for metabolic labeling of nucleic acids. In this review, we summarize the currently available DNA and RNA building blocks, both phosphoramidites and nucleotide triphosphates, for copper-free and bioorthogonal postsynthetic modification strategies.
Topics: Alkynes; Azides; Cycloaddition Reaction; DNA; RNA; Water
PubMed: 32175732
DOI: 10.1021/acs.bioconjchem.0c00072 -
Organic & Biomolecular Chemistry Jul 2022Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-]pyrazol-4(2)-ones or...
Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-]pyrazol-4(2)-ones or 2,5-dihydro-4-pyrazolo[4,3-]quinolin-4-ones Cu(II)-promoted oxidative cascade C-C/C-N bond formation. This protocol has the advantages of atom economy and good functional group tolerance. The primary mechanism studies indicate that the reaction involves a free-radical process as well as terminal alkyne C-H activation.
Topics: Alkynes; Oxidation-Reduction; Oxidative Stress
PubMed: 35792135
DOI: 10.1039/d2ob00639a -
Chemical Record (New York, N.Y.) Jul 2023Enamines are formed by reacting a carbonyl compound with an amine under dehydration conditions. A vast array of transformations has been achieved via preformed enamine... (Review)
Review
Enamines are formed by reacting a carbonyl compound with an amine under dehydration conditions. A vast array of transformations has been achieved via preformed enamine chemistry. Recently, by introducing conjugating double bonds to the enamine functionality, dienamines, and trienamines have propelled the discovery of several previously unattainable remote-site functionalization reactions of carbonyl compounds. Comparatively, alkyne-conjugating enamine analogues have recently shown high potential in multifunctionalization reactions while remaining underexplored. In this account, we systematically summarized and discussed recent advances in synthetic transformations based on ynenamine-containing compounds.
Topics: Catalysis; Stereoisomerism; Amines; Alkynes
PubMed: 37098876
DOI: 10.1002/tcr.202300099 -
Journal of Medicinal Chemistry May 2023Combinatorial library screening increasingly explores chemical space beyond the Ro5 (bRo5), which is useful for investigating "undruggable" targets but suffers...
Combinatorial library screening increasingly explores chemical space beyond the Ro5 (bRo5), which is useful for investigating "undruggable" targets but suffers compromised cellular permeability and therefore bioavailability. Moreover, structure-permeation relationships for bRo5 molecules are unclear partially because high-throughput permeation measurement technology for encoded combinatorial libraries is still nascent. Here, we present a permeation assay that is scalable to combinatorial library screening. A liposomal fluorogenic azide probe transduces permeation of alkyne-labeled molecules into small unilamellar vesicles via copper-catalyzed azide-alkyne cycloaddition. Control alkynes (e.g., propargylamine, various alkyne-labeled PEGs) benchmarked the assay. Cell-permeable macrocyclic peptides, exemplary bRo5 molecules, were alkyne labeled and shown to retain permeability. The assay was miniaturized to microfluidic droplets with high assay quality (' ≥ 0.5), demonstrating excellent discrimination of photocleaved known membrane-permeable and -impermeable model library beads. Droplet-scale permeation screening will enable pharmacokinetic mapping of bRo5 libraries to build predictive models.
Topics: Alkynes; Azides; Catalysis; Copper; Gene Library; Liposomes; Peptides; Pharmacokinetics
PubMed: 37075027
DOI: 10.1021/acs.jmedchem.3c00138 -
International Journal of Molecular... Feb 2022The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is considered to be the most representative ligation process within the context of the "click... (Review)
Review
The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is considered to be the most representative ligation process within the context of the "click chemistry" concept. This CuAAC reaction, which yields compounds containing a 1,2,3-triazole core, has become relevant in the construction of biologically complex systems, bioconjugation strategies, and supramolecular and material sciences. Although many CuAAC reactions are performed under homogenous conditions, heterogenous copper-based catalytic systems are gaining exponential interest, relying on the easy removal, recovery, and reusability of catalytically copper species. The present review covers the most recently developed copper-containing heterogenous solid catalytic systems that use solid inorganic/organic hybrid supports, and which have been used in promoting CuAAC reactions. Due to the demand for 1,2,3-triazoles as non-classical bioisosteres and as framework-based drugs, the CuAAC reaction promoted by solid heterogenous catalysts has greatly improved the recovery and removal of copper species, usually by simple filtration. In so doing, the solving of the toxicity issue regarding copper particles in compounds of biological interest has been achieved. This protocol is also expected to produce a practical chemical process for accessing such compounds on an industrial scale.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper; Cycloaddition Reaction; Triazoles
PubMed: 35216495
DOI: 10.3390/ijms23042383 -
Organic & Biomolecular Chemistry Nov 2022Imidazo[1,2-]benzoazepines were prepared by Brønsted acid-mediated intramolecular alkyne-carbonyl metathesis (ACM). The starting materials, imidazole and benzimidazole...
Imidazo[1,2-]benzoazepines were prepared by Brønsted acid-mediated intramolecular alkyne-carbonyl metathesis (ACM). The starting materials, imidazole and benzimidazole derivatives, were prepared by -alkylation, formylation and Sonogashira cross-coupling reaction. The final intramolecular ACM delivered the final products in good to excellent yields and with a wide tolerance towards functional groups.
Topics: Alkynes; Catalysis; Cyclization
PubMed: 36367114
DOI: 10.1039/d2ob01320g -
Bioconjugate Chemistry Dec 2023Aldehydes are attractive bioorthogonal coupling partners. The ease of manipulation of aldehydes and their orthogonality to other classes of bioorthogonal reactions have...
Aldehydes are attractive bioorthogonal coupling partners. The ease of manipulation of aldehydes and their orthogonality to other classes of bioorthogonal reactions have inspired the exploration of chemistries, which generate irreversible conjugates. Similarly, nitrones have been shown to be potent 1,3-dipoles in bioorthogonal reactions when paired with strained alkynes. Here, we combine the reactivity of nitrones with the simplicity of aldehydes using an -allylglyoxylamide, in a cascade reaction with an -alkylhydroxylamine to produce a bicyclic isoxazolidine. The reaction is found to be catalyzed by 5-methoxyanthranilic acid and proceeds at pH 7 with favorable kinetics. Using the HaloTag7 protein bearing an -alkylhydroxylamine, we show the reaction to be bioorthogonal in a complex cell lysate and to proceed well at the surface of a HEK293 cell. Furthermore, the reaction is compatible with a typical strain-promoted alkyne-azide click reaction. The characteristics of this reaction suggest it will be a useful addition to the pallet of bioorthogonal reactions that have revolutionized chemical biology.
Topics: Humans; HEK293 Cells; Proteins; Nitrogen Oxides; Alkynes; Aldehydes; Azides; Cycloaddition Reaction
PubMed: 38051144
DOI: 10.1021/acs.bioconjchem.3c00463