Showing papers on "Click chemistry published in 2004"
TL;DR: A strain-promoted [3 + 2] cycloaddition between cyclooctynes and azides that proceeds under physiological conditions without the need for a catalyst was demonstrated by selective modification of biomolecules in vitro and on living cells, with no apparent toxicity.
Abstract: Selective chemical reactions that are orthogonal to the diverse functionality of biological systems have become important tools in the field of chemical biology. Two notable examples are the Staudinger ligation of azides and phosphines and the Cu(I)-catalyzed [3 + 2] cycloaddition of azides and alkynes (“click chemistry”). The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Click chemistry obviates the requirement of phosphines, but the Cu(I) catalyst is toxic to cells, thereby precluding in vivo applications. Here we present a strain-promoted [3 + 2] cycloaddition between cyclooctynes and azides that proceeds under physiological conditions without the need for a catalyst. The utility of the reaction was demonstrated by selective modification of biomolecules in vitro and on living cells, with no apparent toxicity.
2,202 citations
1,137 citations
TL;DR: A detailed characterization of the reaction parameters that affect click chemistry-based ABPP is reported and conditions that maximize the speed, sensitivity, and bioorthogonality of this approach are identified.
758 citations
TL;DR: Dendronized linear polymers are prepared from dendritic azides and poly(vinylacetylene) using "click chemistry" and the Cu(I)-catalyzed Huisgen [2 + 3] cycloaddition is quantitative up to the third generation.
Abstract: Dendronized linear polymers are prepared from dendritic azides and poly(vinylacetylene) using "click chemistry." The Cu(I)-catalyzed Huisgen [2 + 3] cycloaddition is quantitative up to the third generation.
572 citations
TL;DR: A microwave-assisted three-component reaction was used to prepare a series of 1,4-disubstituted-1,2,3-triazoles from corresponding alkyl halides, sodium azide, and alkynes, eliminating the need to handle organic azides.
517 citations
TL;DR: In this paper, the copper(I)-catalyzed cycloaddition reaction between azides and alkynes has been employed to make metal-adhesive materials, and the resulting materials were found to possess comparable or superior adhesive strength to standard commercial glues, and structure-activity correlations have identified several important properties of the monomers.
Abstract: The copper(I)-catalyzed cycloaddition reaction between azides and alkynes has been employed to make metal-adhesive materials. Copper and brass surfaces supply the necessary catalytic Cu ions, and thus the polymerization process occurs selectively on these metals in the absence of added catalysts. Alternatively, copper compounds can be added to monomer mixtures and then introduced to reducing metal surfaces such as zinc to initiate polymerization. The resulting materials were found to possess comparable or superior adhesive strength to standard commercial glues, and structure-activity correlations have identified several important properties of the monomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4392–4403, 2004
410 citations
TL;DR: Three new inhibitors were discovered, derived from tacrine and phenylphenanthridinium azides and acetylenes, in the reactions with Electrophorus electricus and mouse AChE, which include the newly formed triazole nexus as a significant pharmacophore.
Abstract: The in situ click chemistry approach to lead discovery employs the biological target itself for assembling inhibitors from complementary building block reagents via irreversible connection chemistry. The present publication discusses the optimization of this target-guided strategy using acetylcholinesterase (AChE) as a test system. The application of liquid chromatography with mass spectroscopic detection in the selected ion mode for product identification greatly enhanced the sensitivity and reliability of this method. It enabled the testing of multicomponent mixtures, which may dramatically increase the in situ screening throughput. In addition to the previously reported in situ product syn-TZ2PA6, we discovered three new inhibitors, syn-TZ2PA5, syn-TA2PZ6, and syn-TA2PZ5, derived from tacrine and phenylphenanthridinium azides and acetylenes, in the reactions with Electrophorus electricus and mouse AChE. All in situ-generated compounds were extremely potent AChE inhibitors, because of the presence of multiple sites of interaction, which include the newly formed triazole nexus as a significant pharmacophore.
388 citations
TL;DR: A fluorogenic probe that is activated by click chemistry, a highly versatile bio-orthogonal and chemoselective ligation reaction which is based on the azide moiety as the functional group is reported.
Abstract: Chemoselective ligation reactions represent a powerful approach for labeling of proteins or small molecules in a biological environment. We report here a fluorogenic probe that is activated by click chemistry, a highly versatile bio-orthogonal and chemoselective ligation reaction which is based on the azide moiety as the functional group. The electron-donating properties of the triazole ring that is formed in the course of the coupling reaction was effectively utilized to modulate the fluorescence output of an electronically coupled coumarin fluorophore. Under physiological conditions the probe is essentially nonfluorescent and undergoes a bright emission enhancement upon ligation with an azide. Time-resolved emission spectroscopy and semiempirical quantum-mechanical calculations suggest that the fluorescence switching is due to an inversion of the energy ordering of the emissive 1(pi,pi*) and nonemissive 3(n,pi*) excited states. The rapid kinetics of the ligation reaction render the probe attractive for a wide range of applications in biology, analytical chemistry, or material science.
325 citations
TL;DR: The aim was to prepare both diene and dienophiles simultaneously, under very mild and environmentally friendly conditions, thus giving the constituents for a stereocontrolled Diels-Alder reaction, which in turn yields compounds 4 to 8.
Abstract: Here we report on our studies on combinations of amino acids and copper(I) for catalyzing multicomponent reactions (MCRs). We aimed to prepare both diene and dienophiles simultaneously, under very mild and environmentally friendly conditions, thus giving the constituents for a stereocontrolled Diels–Alder reaction, which in turn yields compounds 4 to 8. A diversity-oriented synthesis of polysubstituted spirotriones 4 to 6 were assembled from simple substrates like 1-(triphenylphosphanylidene)-propan-2-one, two aldehydes, and cyclic-1,3-diketones through Wittig/Knoevenagel/Diels–Alder and aldol/Knoevenagel/Diels–Alder reaction sequences in one pot under stereospecific organocatalysis. Chemical diversity libraries of polysubstituted spirotrione-1,2,3-traizoles 8 were assembled from simple substrates by means of Wittig/Knoevenagel/Diels–Alder/Huisgen cycloaddition reaction sequences in one pot under stereospecific organo/CuI catalysis. Functionalized dispirolactones such as 6 are biologically active antioxidants and radical scavengers, and spirotrione-1,2,3-traizoles 8 have found wide applications in chemistry, biology, and materials science. Experimentally simple and environmentally friendly, organocatalytic, asymmetric four-component Diels–Alder (AFCDA) reactions of 1-(triphenylphosphanylidene)- propan-2-one, two different aldehydes, and cyclic-1,3-diketones produced diastereospecific and highly enantioselective substituted spirotriones 4 by means of a Wittig/Knoevenagel/Diels–Alder reaction sequence in one pot. Additionally we have developed an organocatalytic, asymmetric three-component Michael (ATCM) reaction of 1-(triphenylphosphanylidene)-propan-2-one, aldehyde, and cyclic-1,3-diketones that produced Michael adducts 15, 16 through a Wittig/Michael reaction sequence in a highly enantioselective one-pot process.
238 citations
TL;DR: In this paper, a monolayers of 11-azido-undecyl-siloxane were prepared on powdered silica and on silicon wafers by the substitution of 11bromo-, undecyl, and were subsequently coupled with three substituted acyclic acid derivatives.
Abstract: Monolayers of 11-azido-undecylsiloxane were prepared on powdered silica and on silicon wafers by the substitution of 11-bromo-undecylsiloxane and were subsequently coupled with three substituted ac...
235 citations
TL;DR: Efficient solution-phase protocols for the high-throughput synthesis of 6-(1,2,3-triazol-1-yl)-dihydropyrimidones are reported and a library of 27 compounds was prepared with 4 points of diversity.
Abstract: Efficient solution-phase protocols for the high-throughput synthesis of 6-(1,2,3-triazol-1-yl)-dihydropyrimidones are reported. The multistep sequence involves the initial bromination of dihydropyrimidones precursors (DHPMs, Biginelli compounds) at the C6-methyl position, using a recyclable polymer-supported brominating agent under rapid flow-through conditions (residence time of 1 min). The 6-bromomethyldihydropyrimidone intermediates were subsequently subjected to a microwave-assisted azidation step (25 min), providing the key 6-azidomethyldihydropyrimidone precursors. In the final step of the sequence, the azides were treated with terminal acetylenes under Cu(I) catalysis (azide-acetylene ligation, "click chemistry") to provide the target 6-(1,2,3-triazol-1-yl)-dihydropyrimidones in a regiospecific fashion (1,4-triazoles) in moderate overall yield utilizing controlled microwave irradiation (20 min). In total, a library of 27 compounds was prepared with 4 points of diversity.
TL;DR: In this article, the triazolylmethyl acrylate (TMA) resin was used for an efficient parallel synthesis of tertiary amines by Michael addition, subsequent quarternization and cleavage by means of β-elimination.
TL;DR: The indirect coupling via a 1,2,3-triazole ring system, of the 2(1H)-pyrazinone scaffold with various saccharides is described, and a microwave-enhanced Cu(I)-catalyzed Huisgen [2 + 3] dipolar cycloaddition reaction is applied, opening the way for the generation of an interesting new class of glycopeptidomimetics.
Abstract: The indirect coupling via a 1,2,3-triazole ring system, of the 2(1H)-pyrazinone scaffold with various saccharides is described. A microwave-enhanced Cu(I)-catalyzed Huisgen [2 + 3] dipolar cycloaddition reaction is applied. This opens the way for the generation of an interesting new class of glycopeptidomimetics.
TL;DR: Cycloaddition of a vitamin D side chain terminal acetylene with phenyl azide and separately with an azide sidechain terminal azide produced the corresponding 1,2,3-triazole monomeric and dimeric analogs of 1α-hydroxyvitamin D 3 in good yields as discussed by the authors.
TL;DR: In this paper, the authors proposed an efficient preparation of CD ring system synthesizers with triazole rings in their side chains based on the formation of the trizole ring from a [3+2]-cycloaddition of a vitamin D side chain terminal azide with a terminal acetylene.
TL;DR: Barry Sharpless drew a big crowd at an educational workshop on homogeneous catalysis at Informex 2004, held last month in Las Vegas as discussed by the authors, and focused instead on his new passion, "click chemistry" where reagents fuse easily irreversibly.
Abstract: NOBEL LAUREATE K. BARRY Sharpless drew a big crowd at an educational workshop on homogeneous catalysis at Informex 2004, held last month in Las Vegas. However, Sharpless talked little of conventional asymmetric catalysis and focused instead on his new passion, "click chemistry" where reagents fuse easily irreversibly. According to the click chemistry manifesto written by Sharpless and his Scripps Research Institute colleagues Hartmuth C. Kolb and M. G. Finn three years ago, reactions that qualify as click chemistry "are modular, [are] wide in scope, give very high yields, generate only inoffensive byproducts that can be removed by nonchromatographic methods, and [are] stereospecific (but not necessarily enantioselective)" [Angew. Chem. Int. Ed., 40 , 2004 (2001)]. In addition, the reaction must consistently give high yields with various starting materials, be easy to carry out, be insensitive to oxygen and water, and use only readily available reagents [Drug Discovery Today, 8 , 1128 (2003)]. The goal, Sh...