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Molecules (Basel, Switzerland) Oct 2022CuAAC (Cu catalyzed azide-alkyne cycloaddition) click-reaction is a simple and powerful method for the post-synthetic modification of organometallic complexes of...
CuAAC (Cu catalyzed azide-alkyne cycloaddition) click-reaction is a simple and powerful method for the post-synthetic modification of organometallic complexes of transition metals. This approach allows the selective introduction of additional donor sites or functional groups to the periphery of the ligand environment. This is especially important if a metalloligand with free donor sites, which are of the same nature as the primary site for the coordination of the primary metal, has to be created. The concept of post-synthetic modification of organometallic complexes by click-reaction is relatively recent and the currently available experimental material does not yet allow us to identify trends and formulate recommendations to address specific problems. In the present study, we have applied the CuAAC reaction for the post-synthetic modification of diimine mononuclear complexes Re(I), Pt(II) and Ir(III) with C≡C bonds at the periphery of the ligand environment and demonstrated that click-chemistry is a powerful tool for the tunable chemical post-synthetic modification of coordination compounds.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper; Cycloaddition Reaction; Ligands
PubMed: 36235030
DOI: 10.3390/molecules27196494 -
Bioconjugate Chemistry Aug 2021Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a modular and bio-orthogonal approach that is being adopted for the efficient synthesis of organic and bioorganic... (Review)
Review
Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a modular and bio-orthogonal approach that is being adopted for the efficient synthesis of organic and bioorganic compounds. It leads to the selective formation of 1,4-disubstituted 1,2,3-triazole units connecting readily accessible building blocks via a stable and biocompatible linkage. The vast array of the bioconjugation applications of click chemistry has been attributed to its fast reaction kinetics, quantitative yields, minimal byproducts, and high chemospecificity and regioselectivity. These combined advantages make click reactions quite suitable for the lead identification and the development of pharmaceutical agents in the fields of medicinal chemistry and drug discovery. In this review, we have outlined the key aspects, the mechanistic details and merits and demerits of the click reaction. In addition, we have also discussed the recent pharmaceutical applications of click chemistry, ranging from the development of anticancer, antibacterial, and antiviral agents to that of biomedical imaging agents and clinical therapeutics.
Topics: Alkynes; Animals; Anti-Infective Agents; Antineoplastic Agents; Azides; Catalysis; Click Chemistry; Copper; Cycloaddition Reaction; Diagnostic Imaging; Drug Discovery; Humans; Triazoles
PubMed: 34319077
DOI: 10.1021/acs.bioconjchem.1c00247 -
Macromolecular Rapid Communications Mar 2021Heterochain polymers such as DNA and proteins are abundant in nature, but they are not ubiquitous in man-made polymers due to the synthetic difficulties. Traditional... (Review)
Review
Heterochain polymers such as DNA and proteins are abundant in nature, but they are not ubiquitous in man-made polymers due to the synthetic difficulties. Traditional polymerization methodologies including chain polymerization, step-growth polymerization, and coordination polymerization all show obvious drawbacks in synthesizing heterochain polymers. The alkyne multicomponent polymerizations (MCPs) developed in the early 2000s open a new door for the synthesis of conjugated heterochain polymers with diverse structures and unique properties. This review presents the progress in novel heterochain polymers constructed by alkyne-based MCPs in the last three years. The unique properties and high-tech applications brought by heteroatoms and MCPs are summarized and perspectives on future directions are also discussed.
Topics: Alkynes; DNA; Humans; Polymerization; Polymers
PubMed: 32808355
DOI: 10.1002/marc.202000386 -
Bioorganic Chemistry Feb 2024Antibody-Drug Conjugates (ADC) are a new class of anticancer therapeutics with immense potential. They have been rapidly advancing in the last two decades. This fast... (Review)
Review
Antibody-Drug Conjugates (ADC) are a new class of anticancer therapeutics with immense potential. They have been rapidly advancing in the last two decades. This fast speed of development has become possible due to several new technologies and methods. One of them is Click Chemistry, an approach that was created only two decades ago, but already is actively utilized for bioconjugation, material science and drug discovery. In this review, we researched the impact of Click Chemistry reactions on the synthesis and development of ADCs. The information about the most frequently utilized reactions, such as Michael's addition, Copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC), Strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), oxime bond formation, hydrazine-iso-Pictet-Spengler Ligation (HIPS), Diels-Alder reactions have been summarized. The implementation of thiol-maleimide Click Chemistry reaction in the synthesis of numerous FDA-approved Antibody-Drug Conjugates has been reported. The data amassed in the present review provides better understanding of the importance of Click Chemistry in the synthesis, development and improvement of the Antibody-Drug Conjugates and it will be helpful for further researches related to ADCs.
Topics: Click Chemistry; Azides; Alkynes; Cycloaddition Reaction; Copper; Maleimides; Sulfhydryl Compounds
PubMed: 37995642
DOI: 10.1016/j.bioorg.2023.106982 -
Macromolecular Rapid Communications Jan 2020The copper-catalyzed azide/alkyne cycloaddition reaction (CuAAC) has emerged as the most useful "click" chemistry. Polymer science has profited enormously from CuAAC by... (Review)
Review
The copper-catalyzed azide/alkyne cycloaddition reaction (CuAAC) has emerged as the most useful "click" chemistry. Polymer science has profited enormously from CuAAC by its simplicity, ease, scope, applicability and efficiency. Basic principles of the CuAAC are reviewed with a focus on homogeneous and heterogeneous catalysts, ligands, anchimeric assistance, and basic chemical principles. Recent developments of ligand design and acceleration are discussed.
Topics: Alkynes; Azides; Carbon; Catalysis; Copper; Cycloaddition Reaction; Ligands; Nitrogen; Phosphorus; Polymers
PubMed: 31631449
DOI: 10.1002/marc.201900359 -
Journal of the American Chemical Society Aug 2022A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a...
A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.
Topics: Alkynes; Amino Acids; Cyclization; Phenylpropionates
PubMed: 35926121
DOI: 10.1021/jacs.2c05892 -
Angewandte Chemie (International Ed. in... Aug 2022Disclosed here is the first geminal (gem-) hydroborative cyclization of enynes. Different from known hydroborative cyclizations, this process adds hydrogen and boron to...
Disclosed here is the first geminal (gem-) hydroborative cyclization of enynes. Different from known hydroborative cyclizations, this process adds hydrogen and boron to the same position, leading to a new reaction mode. With [Cp*RuCl] as catalyst, a range of gem-hydroborated bicyclic products bearing a cyclopropane unit could be rapidly assembled from simple enyne substrates. Control experiments and density functional theory (DFT) calculations provided important insights into the reaction mechanism. Notably, two major competing pathways may operate with substrate-dependence. 1,6-Enynes favor initial oxidative cyclometalation to form a ruthenacyclopentene intermediate prior to engaging hydroborane, while other enynes (e.g., 1,7-enynes) that lack strong propensity toward cyclization prefer initial alkyne gem-(H,B)-addition to form an α-boryl ruthenium carbene followed by intramolecular olefin cyclopropanation. This process also represents the first ruthenium-catalyzed enyne hydroborative cyclization.
Topics: Alkenes; Alkynes; Catalysis; Cyclization; Ruthenium
PubMed: 35596681
DOI: 10.1002/anie.202204319 -
Methods in Molecular Biology (Clifton,... 2023Click chemistry, and particularly azide-alkyne cycloaddition, represents one of the principal bioconjugation strategies that can be used to conveniently attach various...
Click chemistry, and particularly azide-alkyne cycloaddition, represents one of the principal bioconjugation strategies that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields were obtained in the presence of bathophenanthrolinedisulphonate, a water-soluble copper-ion chelator, acting as catalyst. No vesicle leakage was triggered by this conjugation reaction, and the coupled mannose ligands were exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this type of conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent this constraint, an example of alternate copper-free azide-alkyne click reaction has been developed, and it was applied to the anchoring of a biotin moiety that was fully functional and could be therefore quantified. Molecular tools and results are presented here.
Topics: Liposomes; Click Chemistry; Azides; Catalysis; Alkynes; Ligands; Cycloaddition Reaction
PubMed: 36781760
DOI: 10.1007/978-1-0716-2954-3_15 -
Angewandte Chemie (International Ed. in... Apr 2020A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which...
A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which was used to construct the remaining stereogenic centers. A nitrogen atom was introduced either by a four-step sequence involving a Curtius rearrangement, or a three-step sequence featuring a newly developed transformation of a terminal alkyne into a nitrile. Introduction of the guanidine moiety followed by the formation of the heterocyclic system by cascade reactions led to tetrodotoxin.
Topics: Alkynes; Chemistry Techniques, Synthetic; Guanidine; Nitriles; Nitrogen; Tetrodotoxin
PubMed: 31985136
DOI: 10.1002/anie.201916611 -
Journal of the American Chemical Society May 2022The hexadehydro-Diels-Alder (HDDA) reaction converts a 1,3-diyne bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates upon thermal activation....
The hexadehydro-Diels-Alder (HDDA) reaction converts a 1,3-diyne bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates upon thermal activation. With only a few exceptions, this unimolecular cycloisomerization requires, depending on the nature of the atoms connecting the diyne and diynophile, reaction temperatures of 80-130 °C to achieve a convenient half-life (, 1-10 h) for the reaction. In this report, we divulge a new variant of the HDDA process in which the tether contains a central, quaternized nitrogen atom. This construct significantly lowers the activation barrier for the HDDA cycloisomerization to the benzyne. Moreover, many of the ammonium ion-based, alkyne-containing substrates can be spontaneously assembled, cyclized to benzyne, and trapped in a single-vessel, ambient-temperature operation. DFT calculations provide insights into the origin of the enhanced rate of benzyne formation.
Topics: Alkynes; Ammonium Compounds; Cycloaddition Reaction; Diynes; Temperature
PubMed: 35442671
DOI: 10.1021/jacs.2c00877