Expedient, regioselective C-H chalcogenation of 3,4-dihydro-1,4-benzoxazines using a palladium-copper catalyst.

The palladium-catalysed regioselective C-H chalcogenation of benzoxazines with disulfides and diselenides in air has been described. In this protocol, palladium acetate serves as the catalyst in conjunction with copper as an oxidizing agent. Through this approach, a wide array of sulfenylation and selenylation reactions of benzomorpholines have been effected, yielding results ranging from good to excellent. Thus, the established procedure demonstrates superb regioselectivity and a strong tolerance towards various functional groups and is suitable for gram-scale synthesis. Additionally, this synthetic approach offers a practical and convenient pathway for late-stage functionalization leading to the Rosenmund-von Braun reaction.

Visible-Light-Driven Regioselective Decarboxylative Acylation of N-Methyl-3-phenylquinoxalin-2(1H)-one by Dual Palladium-Photoredox Catalysis Through C-H Activation.

We report herein an efficient visible-light-promoted approach for the regioselective decarboxylative C-H acylation of N-methyl-3-phenylquinoxalin-2(1H)-ones using α-oxo-2-phenylacetic acids via dual palladium-photoredox catalysis. The reactions were carried out at room temperature in the presence of 24 W blue LEDs. The established protocol tolerated a wide range of functional groups and enabled the synthesis of several acylated N-methyl-3-phenylquinoxalin-2(1H)-ones in good to excellent yields. The proposed mechanism for this transformation was supported by control experiments.

Rhodium-catalyzed selenylation and sulfenylation of quinoxalinones 'on water'.

A rhodium-catalysed, regioselective synthetic methodology for selenylation and sulfenylation of 3-phenyl quinoxolinones has been developed through N-directed C-H activation in the presence of silver triflimide, and silver carbonate using dichalcogenides 'on water'. The methodology has been proven to be efficient, regioselective and green. Using this method, a range of selenylations and sulfenylations of the substrates has been carried out in good to excellent yields. Further, late-stage functionalisation produced potential anti-tumour, anti-fungal and anti-bacterial agents making these compounds potential drug candidates.

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles.

A microwave-assisted synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles from a phenylazide, propargyloxybenzaldehyde and a 1,2-diaminobenzene is proposed.

O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis.

Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations.

Identification of small peptides inhibiting the integrase-LEDGF/p75 interaction through targeting the cellular co-factor.

The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This process is mediated by the viral enzyme integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 has been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Recently, circular peptides were identified that bind to the C-terminal domain of IN and disrupt the interaction with LEDGF/p75. Starting from the circular peptides, we identified a short peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low µM concentration through its binding to the IN binding site of LEDGF/p75. This discovery can lead to the synthesis of peptidomimetics with high anti-HIV activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN.

Palladium-catalyzed copper(I)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling.

The application of a palladium-catalyzed Cu(I)-mediated Liebeskind-Srogl protocol for the decoration of the 2(1H)-pyrazinone scaffold resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling.

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.

Copper(II)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling.

[reaction: see text] Optimized conditions for the decoration of the 2(1H)-pyrazinone scaffold were developed by applying the Chan-Lam protocol. It was demonstrated that this Cu(II)-mediated cross-coupling reaction resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling at 0 degrees C, applying a mixture of bases Et(3)N/pyridine.