Synthesis of crosslinking amino acids by click chemistry

Crosslinking amino acids are naturally existing protein crosslinkers. Herein, we described the synthesis of several novel bis-amino acids constituted of serine, alanine, lysine, and tyrosine with click chemistry. The Huisgen 1,3-dipolar cycloadditions between azido- and alkyne-functionalized amino acids can be easily realized in the presence of catalytic amount of CuSO₄ and Na ascorbate. In addition, fluorescent bis-amino acid derivatives have also been prepared using anthracene, fluorescein, and benzothiadiazole as fluorophores. With symmetrical bis-alkyne benzothiadiazole, it was possible to synthesize asymmetrical derivative bearing two different amino acid moieties.     

Synthesis of new copper(I)-complexed rotaxanes via click chemistry

The Cu(I)-catalyzed dipolar cycloaddition of azides and terminal alkynes (‘click’ chemistry) has been used as a mild and efficient stoppering reaction for the preparation of new copper(I)-complexed rotaxanes.     

Synthesis of glycidyl triazolyl polymers using click chemistry

The glycidyl azide polymers converted easily to glycidyl 1,2,3-triazolyl polymers by the click chemistry in good to high yields. These reactions are affected deeply by the electron effects. The electron donating groups made the reaction faster.     

Preparation of novel chiral stationary phase based on click chemistry for ligand exchange chromatography

Click chemistry was applied to immobilize L-proline derivative onto azide-modified silica gel to give a novel chiral stationary phase(denoted as click-CSP) for ligand exchange chromatography.The developed protocol combines the benefits of operational simplicity,exceptionally mild conditions and high surface loadings.The enantioselectivityαof some DL-amino acids on the click-CSP were found to be in the range from 1.13 to 3.46.The chromatographic resolutions of some DL-amino acids and the stability study f...     

Fixed-charge labels for simplified reaction analysis: 5-hydroxy-1,2,3-triazoles as byproducts of a copper(I)-catalyzed click reaction

High-resolution multistage mass spectrometric studies of isotope-labelled derivatives of a fixed-charge labelled sugar triazole assisted the identification of 5-hydroxy-1,2,3-triazoles as byproducts of the copper(I)-catalyzed cycloaddition of azides and terminal alkynes. Reaction optimization with inclusion of the auxiliary ligand, tris(benzyltriazolylmethyl)amine furnished an improved ligation protocol in which formation of the 5-hydroxytriazole is mitigated.     

Synthesis of peptide dendrimers with polyhedral oligomeric silsesquioxane cores via click chemistry

Inorganic polyhedral oligomeric silsesquioxane (POSS) was used as the core for the synthesis of poly(Llysine) peptide dendrimer via copper-catalyzed azide-alkyne click chemistry. The inorganic/organic composite dendrimer was characterized by MS, 1H NMR, FTIR, GPC and DLS.     

Synthesis of N-propynyl analogues of peptide nucleic acid (PNA) monomers and their use in the click reaction to prepare N-functionalized PNAs

Application of the click reaction for coupling a 2-(2-aminoethoxy)ethoxy (AEE) function to thyminyl, cytosinyl and adeninyl peptide nucleic acid (PNA) monomer analogues bearing a N-propynyl group, in place of the original N-2-aminoethyl moiety, has been explored. The N-propynyl PNA analogues were prepared from glycine ethyl ester hydrochloride and the structure of the thyminyl derivative was confirmed by X-ray diffraction. These monomers were employed in click reactions with Boc-protected AEE azide to afford the corresponding triazolyl-linked PNA-AEE conjugates in yields ranging from 64 to 76%. [1,4]-Regiochemistry was verified from a NOESY correlation experiment.     

Synthesis of novel aromatic ether polymers containing perfluorocyclobutyl and triazole units via click chemistry

The synthesis and characterization of a novel class of linear aromatic ether polymers containing perfluorocyclobutyl and triazole unites is described. These polymers were prepared from the click chemistry (the copper-catalyzed Huisgen's 1,3-dipolar cycloaddition) of new monomer 1,2-bis(4-azidomethylphenoxy) perfluorocyclobutane and bisethynyl compounds.     

Structure and behaviour of the free radicals generated in gamma irradiated amino acid and iminodiacetic acid derivatives

An EPR study has been carried out to investigate the structure and behaviour of the free radical formed γ-irradiated l-alaninamide hydrochloride, dl-glutamic acid monohydrate and N-(2-carboxyethyl) iminodiacetic acid powders at room temperature. The observed paramagnetic species have been attributed to the CH(3)?HCONH(2), HOOCCH(2)CH(2)?HCOOH and HOOCCH(2)CH(2)N?HCH(2)(COOH)(2) radicals, respectively. Some spectroscopic properties and suggestions concerning possible structure of the radicals were also discussed in this study.     

Preparation of azidoaryl- and azidoalkyloxazoles for click chemistry

A series of azidoaryl- and azidoalkyl(diphenyl)oxazole scaffolds were warranted for biofilm inhibition studies. Cyclization of azidoaryl- or azidoalkyl esters of benzoin with ammonium acetate in acetic acid gives 2-azidoaryl- or 2-azidoalkyl-4,5-diphenyloxazoles. The azidoaryl esters are prepared from the corresponding azidocarboxylic acids/acid chlorides while the azidoalkyl esters are prepared from the corresponding haloalkyl esters.     

Synthesis of new, BODIPY-based sensors and labels

New, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye based thiol-reactive fluorescent label, fluorescent amino acid, and fluoroionophore compounds with 540-560 nm emission are described. Combination of a BODIPY dye with a nitronyl nitroxide or an imino nitroxide or a bifunctional pyrroline nitroxide furnished a nitric oxide, a redox sensitive molecule and a double (spin and fluorescence) label, respectively.     

Efficient and tunable synthesis of new polydentate bifunctional chelating agents using click chemistry

Two novel bifunctional chelating agents, which are bistriazole-based polyaminocarboxylic acids, have been designed and synthesised in high yields. An elegant synthetic approach using the Cu-catalysed azide-alkyne cycloaddition has been developed. This convenient route could be employed for the synthesis of a variety of polydentate bifunctional chelators.     

Synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones through copper(I)-catalyzed interrupted click reaction

A Cu-catalyzed interrupted click reaction for the synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones is developed. The reaction between the terminal alkynes with azides and pentafluoropropionic or heptafluorobutyric anhydride proceeds smoothly to afford the corresponding pentafluoroethylated or heptafluoropropyled products in good yields. This protocol is applicable to various types of substrates including arylacetylenes and aliphatic azides having electron-rich and electron-deficient groups. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 3-perfluoroalkyl-substituted 1,2,4-triazinones. Some of the title compounds showed fungicidal activity against cucumber downy mildew (CDM).     

Peptide ligation through click chemistry for the generation of assembled and scaffolded peptides

The synthesis of [1,2,3]-triazoles through copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition was examined for its utility to generate assembled and scaffolded peptides from peptide and scaffold precursors, which were N-terminally modified with azido and alkyne moieties, respectively.     

Efficient synthesis of a labile copper(I)-rotaxane complex using click chemistry

Copper(I)-induced threading of 5,5′-diazidomethyl-2,2′-bipyridine through a coordinating ring followed by reaction of a propargyl ether attached to a stopper group leads to the desired rotaxane in 62% yield. The reaction is carried out under the ‘click chemistry’ conditions with 0.75 equiv of additional copper(I).     

Synthesis,curing and properties of poly(phthalazione ether sulfone ketone) copolymers crosslinked by click chemistry

Functionalized poly(phthalazinone ether sulfone ketone) was synthesized by successive chloromethylation and azidation, followed by curing reaction with the propargyl end-groups of various molecular weight crosslinking agents in the presence of Cu(Ⅰ) catalyst via the azide-alkyne click reaction. The influences of the chain length of crosslinking agents on the poly(phthalazinone ether sulfone ketone) system were studied. FTIR and DSC tests demonstrated certain crosslinking by azide-alkyne reaction with the formation of triazole ring. DSC results showed that curing temperature shifted to lower temperatures considerably in the presence of Cu(Ⅰ) catalyst. TGA showed cured polymers were of much higher thermal stability, including higher thermal decomposition temperatures and higher char-yielding properties. After being cured, the polymers became insoluble in organic solvents and the gel fraction of the cured polymers exceeded 71%. Wide-angle X-ray diffraction results indicated there was a short distance order in the poly(ether sulfone)(PES) main chain except for the azido methyl poly(phthalazinone ether sulfone ketone) and 4,4'-bis(2-propynyloxy) biphenyl( AMPPESK-BP) system.     

点击化学法快速合成氨基酸功能化的环糊精聚轮烷

通过叠氮-炔环加成点击反应制备了各种氨基酸功能化的生物相容性β-环糊精封端的α-环糊精聚轮烷.利用FTIR和氢核磁共振谱对产物的结构进行了表征.结果证明对于空间位阻较小的分子,点击反应能够在很短的时间(几分钟)内达到近100%的转化率.点击化学为功能化聚轮烷的制备提供了快速有效的新途径.     

Fluorogenic dual click derived bis-glycoconjugated triazolocoumarins for selective recognition of Cu(II) ion

Carbohydrate based fluorescent sensors S1 and S2 have been developed by fluorogenic dual click chemistry and are characterized by various spectroscopic techniques. Both the fluorescent probes displayed highly selective detection of Cu²⁺ ions by means of fluorescence quenching. The job plot experiment suggested 1:1 complexation of probes S1 and S2 with Cu²⁺ ions having detection limit of 6.99 μM and 7.30 μM, respectively. The binding constants for S1-Cu²⁺ and S2-Cu²⁺ complexation were evaluated to be 3.34 × 10³ M⁻¹ and 5.93 × 10³ M⁻¹, respectively.     

Facile and efficient Lewis acid catalyzed synthesis of an asymmetric tetrazine useful for bio-orthogonal click chemistry applications

Bio-orthogonal tetrazine click reactions have recently attracted significant interest for applications spanning biological imaging, cancer targeting, and biomaterials science. Here, we report a simple and efficient two-step scheme for the synthesis of an asymmetric tetrazine molecule containing a carboxylic acid handle for subsequent macromolecular conjugation. Yields as high as 75% were achieved using as little as 0.005 equiv of nickel triflate catalyst, which is a significant improvement over previous methodologies.     

Combination of click chemistry and sulfonamides to develop three-armed triazole compounds

Fragment-based drug discovery is a valuable tool in hit identification, as well as the combination of different small fragments showing a minimal binding activity against biological receptors or enzymes to give merged hits. A high number of fragments on the same scaffold improve the probability to find a candidate showing single- or multi-target affinities. A rapid and versatile approach for synthesizing libraries of densely fragment-functionalized scaffolds is reported. Many fragments were assembled in few steps around a triazole ring starting from amino alcohols and other readily available building blocks. A binding assay against integrin α_vβ₃ was used as a test-bed in order to demonstrate the potential of such an approach in hit discovery strategies.