Conjugation of aminoadamantanes by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition

Four variants of conjugation of aminoadamantanes with 1,2,3-triazole- and ditriazolecontaining spacers by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition of azido- and propargyl-containing aminoadamantanes were suggested.     

Modification of tetrahydrocarbazoles with pharmacophore ligands by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition

A synthetic approach to the modification of tetrahydrocarbazoles with pharmacophore ligands (carbazole, tetrahydrocarbazole, and phenothiazine) was proposed based on the coppercatalyzed alkyne-azide 1,3-dipolar cycloaddition of azide-containing tetrahydrocarbazoles and propargyl-containing carbazole, tetrahydrocarbazole, and phenothiazine.     

Effect of temperature on triazole and bistriazole formation through copper-catalyzed alkyne-azide cycloaddition

Temperature is an important factor in the copper catalyzed alkyne azide cycloaddition under oxidative conditions. 1,2,3-Triazoles were obtained in high yields when several alkynes and azides were reacted at methanol reflux using catalytic amounts of both copper iodide and sodium hydroxide. On the other hand, bistriazoles were major products when reactions were performed at −35 °C using excess sodium hydroxide.     

A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne-azide cycloaddition reactions

We report a facile synthesis of fused dihydrotriazolo[1,5-a]pyrazinones and triazolobenzodiazepines by an Ugi/alkyne-azide cycloaddition synthetic sequence. The coupling of the Ugi multi-component reaction with the intramolecular alkyne-azide cycloaddition provides access to highly functionalized heterocyclic ring systems in two steps from easily available starting materials in excellent overall yields.     

Synthesis of pyrrole and indole quinoxalinone and oxazinone derivatives by intramolecular copper-catalyzed reactions

Intramolecular N-arylation of pyrrole and indole carboxamides and carboxylates linked with a pendant haloarene by Cu-catalyzed reactions to synthesize pyrrole and indole quinoxalinone and oxazinone derivatives is reported. The ring closure reactions were carried out by conventional heating and MW irradiation. The use of conventional heating affords moderate to good yields of the quinoxalinone and oxazinone derivatives (34-72%), while by using MW heating the best results are obtained (41-99%).     

Kinetic resolution by copper-catalyzed azide-alkyne cycloaddition

The use of chiral pybox ligands imparts enantioselectivity to the Cu^I-catalyzed azide-alkyne cycloaddition reaction, in the form of kinetic resolution of α-chiral azides and desymmetrization of gem-diazides. While levels of selectivity are modest, the results show unequivocally that the process benefits from ligand-accelerated catalysis.     

Fast copper-free click DNA ligation by the ring-strain promoted alkyne-azide cycloaddition reaction

Templated DNA strand ligation by the ring-strain promoted alkyne-azide [3+2] cycloaddition reaction is very fast; with dibenzocyclooctyne, the reaction is essentially complete in 1 min. It is inhibited by the presence of a single mismatched base pair suggesting applications in genetic analysis.     

Construction of di-scFv through a trivalent alkyne-azide 1,3-dipolar cycloaddition

Heterofunctional azide and alkyne PEG-linkers have been synthesized and site specifically conjugated to scFv via a reactive thiol functionality; two scFv were coupled by copper catalyzed 1,3-dipolar cycloaddition to make divalent scFv (di-scFv) with an inter-scFv distance defined to provide divalent binding; antigen binding was maintained for the di-scFv construct and increased several times compared to that of the parent scFv; the cycloaddition reaction reported herein represents an important ligation strategy to covalently link macromolecular proteins and retain sensitive structural conformations.     

Copper-free click biofunctionalization of silicon nitride surfaces via strain-promoted alkyne-azide cycloaddition reactions

Cu-free "click" chemistry is explored on silicon nitride (Si(3)N(4)) surfaces as an effective way for oriented immobilization of biomolecules. An ω-unsaturated ester was grafted onto Si(3)N(4) using UV irradiation. Hydrolysis followed by carbodiimide-mediated activation yielded surface-bound active succinimidyl and pentafluorophenyl ester groups. These reactive surfaces were employed for the attachment of bicyclononyne with an amine spacer, which subsequently enabled room temperature strain-promoted azide-alkyne cycloaddition (SPAAC). This stepwise approach was characterized by means of static water contact angle, X-ray photoelectron spectroscopy, and fluorescence microscopy. The surface-bound SPAAC reaction was studied with both a fluorine-tagged azide and an azide-linked lactose, yielding hydrophobic and bioactive surfaces for which the presence of trace amounts of Cu ions would have been problematic. Additionally, patterning of the Si(3)N(4) surface using this metal-free click reaction with a fluorescent azide is shown. These results demonstrate the ability of the SPAAC as a generic tool for anchoring complex molecules onto a surface under extremely mild, namely ambient and metal-free, conditions in a clean and relatively fast manner.     

Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction

The attachment of labels onto DNA is of utmost importance in many areas of biomedical research and is valuable in the construction of DNA-based functional nanomaterials. The copper(I)-catalyzed Huisgen cycloaddition of azides and alkynes (CuAAC) has recently been added to the repertoire of DNA labeling methods, thus allowing the virtually unlimited functionalization of both small synthetic oligonucleotides and large gene fragments with unprecedented efficiency. The CuAAC reaction yields the labeled polynucleotides in very high purity after a simple precipitation step. The reviewed technology is currently changing the way in which functionalized DNA strands are generated cost-efficiently in high quality for their application in molecular diagnostics systems and nanotechnological research.     

Regiospecific synthesis of quinizarin derivatives by cycloaddition

Cycloadditionof ($\text{E}$)-1,1,4-trimethaxy-1,3-butadiene (1) to naphthoquinones affords regiospecific syntheses of derivatives of 1,4-dihydroxyanthraquinone including the mould metabolites helminthosporin (21) and cynodontin (22).     

Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition

A procedure is presented for copper(I)-catalyzed [3+2] cycloaddition of nucleosides and nucleotides in near-quantitative yield. Azido-alkyne cycloaddition was applied for the preparation of a range of adenosine dimers and derivatives with versatile functionality, as well as for the smooth condensation of two oligonucleotide strands. The described technology may find valuable application in the synthesis of oligonucleotide dimers and conjugates.     

Synthesis of fullerene glycoconjugates via a copper-catalyzed Huisgen cycloaddition reaction

The synthesis of fullerene-carbohydrate conjugates using a copper-catalyzed [3+2] cycloaddition reaction to facilitate the union of an azido-functionalized sugar and a pentaalkynyl[60]fullerene is straightforward. Thus, fullerenes bearing five oligosaccharides such as Gb3-trisaccharide can be readily accessed. Nanometer-scale molecular architectures presenting as many as 15 sugar moieties in C5-symmetry are readily produced. The cycloaddition reaction proceeds quantitatively under mild conditions without the need to protect the sugar hydroxyl groups.     

Photo-oxidation of indole derivatives

The UV irradiation of 2- and 3-methylindoles in acetic acid leads to the formation of the corresponding indole-carboxaldehydes as the major products, whereas the employment of ethanol as solvent causes the cleavage of the C₂2-C₃ bond, giving o-acylaminophenylketones.Some aspects of these photo-reactions are discussed.     

A new approach to the efficient indole synthesis by allene intramolecular cycloaddition

A new development of efficient indole synthesis via allene intramolecular cycloaddition strategy is described.     

Synthesis of alkyl indole derivatives

Condensation of arylamines with α-halogenoketone afforded the intermediate anilino-ketones which on direct cyclization furnished the corresponding alkylindoles. Synthesis of 2,3,5-trimethyl-4,7-dimethoxyindole (5a) and 2,3,6-trimethyl-7-methoxyindole (5b) is described. Earlier (1) synthesis of 2,3-dimethyl-4,7-dimethoxyindole and 1,2,3-trimethyl-4,7-dimethoxy-indole is reported.     

Electrosynthesis of fluorinated indole derivatives

Anodic fluorination of various N-acetyl-3-substituted indole derivatives was successfully carried out in Et₄NF-4HF/MeCN to provide the corresponding trans-2,3-difluoro-2,3-dihydroindoles exclusively or selectively. Treatment of difluorinated products with a base provided monofluoroindole derivatives or monofluoroindoline derivative depending on the substituents at the 3-position.