Transition metal-catalyzed orthogonal solid-phase decoration of the 2(1H)-pyrazinone scaffold using a sulfur linker

A new transition metal-catalyzed orthogonal solid-phase protocol for the synthesis of highly substituted 2(1H)-pyrazinones was developed, on the basis of Chan-Lam arylation and Liebeskind-Srogl cross-coupling reactions. This strategy opens the way for the generation of small libraries of 2(1H)-pyrazinone analogues for biological screening.     

Solid-phase synthesis of the 2(1H)-pyrazinone scaffold: a new approach toward diversely substituted heterocycles

The first solid-phase synthesis of the 2(1H)-pyrazinone scaffold is described. The diversity at position C6 of the pyrazinone ring is determined by the choice of the starting aldehyde. Microwave-enhanced transition metal-catalyzed reactions allow easy introduction of a variety of substituents at the C3 position. This opens a way for the generation of libraries of diversely substituted 2(1H)-pyrazinones that will be screened for biological activities.     

Facile decoration of functionalized single-wall carbon nanotubes with phthalocyanines via "click chemistry"

We describe the functionalization of single-wall carbon nanotubes (SWNTs) with 4-(2-trimethylsilyl)ethynylaniline and the subsequent attachment of a zinc-phthalocyanine (ZnPc) derivative using the reliable Huisgen 1,3-dipolar cycloaddition. The motivation of this study was the preparation of a nanotube-based platform which allows the facile fabrication of more complex functional nanometer-scale structures, such as a SWNT-ZnPc hybrid. The nanotube derivatives described here were fully characterized by a combination of analytical techniques such as Raman, absorption and emission spectroscopy, atomic force and scanning electron microscopy (AFM and SEM), and thermogravimetric analysis (TGA). The SWNT-ZnPc nanoconjugate was also investigated with a series of steady-state and time-resolved spectroscopy experiments, and a photoinduced communication between the two photoactive components (i.e., SWNT and ZnPc) was identified. Such beneficial features lead to monochromatic internal photoconversion efficiencies of 17.3% when the SWNT-ZnPc hybrid material was tested as photoactive material in an ITO photoanode.     

Synthesis of highly functionalized 2(1H)-pyrazinone 3-carboxamide scaffolds

Synthesis of highly functionalized 2(1H)-pyrazinone 3-carboxamide derivatives is reported. A one-pot, two-step process including the base-mediated reaction of N,N-disubstituted aminoacetonitrile derivatives 18 with 3,5-dihalo-2(1H)-pyrazinones 1 afforded substituted aminoacetonitrile pyrazinone derivative 19, which on subsequent oxidation followed by transamidation of the resulting intermediate with primary or secondary amines gave the corresponding highly functionalized 2(1H)-pyrazinone 3-carboxamide derivatives 21.     

Synthesis of 2(1H)-pyrazinone phosphonates via an Arbuzov-type reaction

A simple and catalyst-free method for the synthesis of phosphonated 2(1H)-pyrazinones is described starting from 3,5-dichloropyrazinones. The method also works for 3-bromo- and 3-iodopyrazinones. Classical heating conditions as well as microwave-enhanced reaction conditions were tested.     

Combining Biginelli multicomponent and click chemistry: generation of 6-(1,2,3-triazol-1-yl)-dihydropyrimidone libraries

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.     

Azide-derivatized gold nanorods: functional materials for "click" chemistry

We describe herein the synthesis of functional gold nanorods suitable for carrying out "click" chemistry reactions. Gold nanorods modified with a copolymer containing sulfonate and maleic acid groups have been conjugated to a bifunctional azide molecule (amine-PEG-azide). The maleic acid molecules in the copolymer participate in carbodiimide-mediated amide bond formation with amine groups of the azide linker, whereas the sulfonate groups prevent nanorod aggregation in water. Spectroscopic and zeta-potential measurements have been used to confirm the successful surface modification of the gold nanorods. These azide-functionalized nanorods can carry out chemical reactions based on click chemistry. As a case study, we have demonstrated the "clicking" of azide-nanorods to an acetylene-functionalized enzyme, trypsin, by a copper-catalyzed 1,3-dipolar cycloaddition reaction. The enzyme is not only stable after bioconjugation but is also biologically active, as demonstrated by its digestion of the protein casein. For comparison, the biological activity of trypsin conjugated to gold nanorods by two other commonly used methods (carbodiimide-mediated covalent attachment via amide bond formation and simple electrostatic adsorption) has been studied. The enzyme conjugated by click chemistry demonstrates improved biological activity compared with other forms of bioconjugation. This general and simple approach is easy, specific with higher yields, environmentally benign, and applicable to a wide range of analytes and biomolecules.     

New tetramethylthiepinium (TMTI) for copper-free click chemistry

A new derivative of the strained 3,3,6,6-tetramethylthiacycloheptyne (TMTH) bearing a functional handle is reported. Following an optimized synthesis, the handle was introduced by mild alkylation of the sulphur atom. The resulting functionalized strained 4,5-didehydro-3,3,6,6-tetramethyl-2,3,6,7-tetrahydrothiepinium (TMTI) proved to be stable and underwent extremely fast [3+2] cycloaddition reaction with benzyl azide in both organic and aqueous solvents. The reaction was equally efficient in cell lysate and serum and therefore opens interesting prospects for chemical-biology applications.     

A convenient microwave-assisted desulfitative dimethylamination of the 2(1H)-pyrazinone scaffold using N,N-dimethylformamide

A convenient microwave-assisted methodology is developed for the generation of 5-chloro-3-(dimethylamino)pyrazin-2(1H)-ones. The method entails a chemoselective desulfitative removal of a phenylthioether bond upon DMF/H₂O treatment in the presence of sodium carbonate, yielding the desired compounds in 73-96%.     

Synthesis of 3-miktoarm stars and 1st generation mikto dendritic copolymers by "living" radical polymerization and "click" chemistry

The facile synthesis of 3-miktoarm star polymers and 1st generation mikto polymeric dendrimers using atom transfer radical polymerization (ATRP) and "click" chemistry is demonstrated. ATRP was used to synthesize near uniform polymers with Br chain ends, which were easily converted into azido groups. These polymer chains were then attached to a trifunctional alkyne molecule (tripropargylamine) using click reactions in a variety of ways to make the miktoarm stars and miktoarm polymeric dendrimers.     

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.     

Expanding the application scope of glycosidases using click chemistry

Glycosidase-mediated glycosylation of alkynyl alcohols and azide-containing alcohols was followed by a click reaction, affording various types of triazole glycosides. The activities of triazole glycosides detected in subsequent bioassays show that this procedure is a feasible approach to the development of anti-fungal drugs.     

Paenibacillin A,a new 2(1H)-pyrazinone ring-containing natural product from the endophytic bacterium Paenibacillus sp. Xy-2

A new 2(1H)-pyrazinone ring-containing natural product, paenibacillin A (1), together with five known diketopiperazine derivatives 2–6 and two known isoflavones 7–8, was isolated from the culture of an endophytic bacterium Paenibacillus sp. Xy-2. The structure of compound 1 was elucidated by extensive spectral methods, including UV, IR, HR-ESI-MS, 1D and 2D NMR and ECD experiments. Compound 1 exhibited moderate cytotoxicity against HL-60 cell line with IC₅₀ value of 50.48 μM.     

Studies on pyrazines. 13 . Chlorination of 1-hydroxy-2(1H)-pyrazinones with phosphoryl chloride. Formation of 2,5-dichloro-3-phenylpyrazine from 1-hydroxy-3-phenyl-2(1H)-pyrazinone

The chlorination of 1-hydroxy-3-phenyl-2(1H)-pyrazinone with phosphoryl chloride proceeded to 5-chloro-3-phenyl-2(H)-pyrazinone or 2,5-dichloro-3-phenylpyrazine on heating to elevated temperatures. To define the mechanism of the novel formation, reactions of the parent or methyl-substituted 1-hydroxy-2(1H)-pyraz-inones with the same reagent were investigated.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)dione (isatoic anhydrides) 1. The synthesis of N-substituted 2H-3,1-benzoxazine-2,4(1H)diones

Three methods for the preparation of N-substituted 2H-3,1-benzoxazine-2,4(1H)diones (isatoic anhydrides) (1) utilizing 2-chloro-, 2-nitrobenzoic acids and N-unsubstituted isatoic anhydrides as starting materials, are described.     

2D assembly of non-interacting magnetic iron oxide nanoparticles via"click" chemistry

Azide-terminated magnetic iron oxide nanoparticles have been assembled in 2D on alkyne-terminated self-assembled monolayers (SAMs) by the copper(i) catalyzed alkyne-azide cycloaddition (CuAAC) "click" reaction; the kinetics of the reaction is an important parameter to control the interparticle distance and thus the dipolar interactions.     

Advance of click chemistry in anion exchange membranes for energy application

Click chemistry has attracted tremendous attention in polymer synthesis due to its high efficiency, considerable yield, and simple synthesis/work-up procedures. Among the various functional polymer materials prepared by click chemistry, anion exchange membrane (AEM) is a kind of polyelectrolyte which contains cations attached to the polymer skeleton. Click chemistry not only provides facile pathways for the preparation of AEMs but also generates diverse architectures of AEMs with robust performance. The commonly used click chemistry in AEMs consists of: (i) Diels-Alder reaction, (ii) thiol-ene, and (iii) Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). This review will focus on the advance of click chemistry in the preparation of AEMs, especially synthetic approaches for different AEMs and their corresponding application in energy-related fields, such as fuel cells, redox flow battery, electrodialysis, and so on.     

"Thiol-ene" click chemistry: a facile and versatile route for the functionalization of porous polymer monoliths

The preparation of porous polymer monoliths with dodecyl and zwitterionic functionalities via the "thiol-ene" click chemistry of thiol-containing monoliths with both hydrophobic and polar methacrylate "ene" monomers has been demonstrated. Selected separations confirmed the excellent potential of these monoliths in chromatography.