Organic & Biomolecular Chemistry最新文献

We present a method for synthesizing N-benzyl pyridones from para-quinone methides (p-QMs) and 2- or 4-hydroxy pyridines in the presence of a base at room temperature. The reaction proceeds through 1,6-Michael addition reaction. Simple operation, good to excellent yields, broad substrate scope, and good functional group tolerance are the salient features of the developed methodology. The synthesized N-benzyl pyridones displayed significant in vitro blood-stage antiplasmodial activity at sub-micromolar concentration.

A series of enone-hydrazones were synthesized through the reaction of enaminones with hydrazones under solvent-free, additive-free, and metal-catalyst-free conditions. The target products were obtained in high yields, with outstanding group tolerance, stereoselectivity, and chemical selectivity. In this work, a series of novel enaminone skeleton compounds were synthesized, and deuteration experiments showed that enone-hydrazones have different properties from traditional electron-deficient enketones.

Correction for 'Cu(II)-Mediated aerobic oxidative synthesis of sulfonated chromeno[4,3-c]pyrazol-4(2H)-ones' by Quan Zhou et al., Org. Biomol. Chem., 2022, 20, 5575-5581, https://doi.org/10.1039/D2OB00639A.

For the first time, the photochemical behavior of aryl-substituted 2,3-dihydropyrazine 1,4-dioxides was investigated. A common feature of all observed photoprocesses is the conversion of nitrone moieties into an oxaziridine ring to give substituted bi- or polycyclic systems. It was shown that the direction of the reaction depends on the irradiation wavelength and the employed solvent. For instance, the use of 365 nm UV light leads to the cyclization of both nitrone moieties. In contrast, visible-light irradiation (450 nm) allows one to regiospecifically utilize an aldonitrone unit to form 7-oxa-1,4-diazabicyclo[4.1.0]hept-4-ene 4-oxide derivatives. Generally, the oxaziridine ring possesses high reactivity and can be transformed in situ by various reagents. The molecular and crystal structures of the representatives of both bicyclic systems were solved for the first time with X-ray diffraction analysis.

Despite recent advances in H/D exchange, the effective deuteration of polyarenes remains challenging, due to their insolubility and hydrophobicity. This study presents a concept proofing of a mechanochemically facilitated direct H/D exchange. The silver-catalyzed deuteration of heteroarenes was promoted smoothly within 99 minutes of grinding, with heavy water as the deuterium source.

Annulations through dual C-H activation represent a powerful tool to selectively assemble multi-cyclic scaffolds. We present herein a palladium-catalyzed ortho-/meta-C-H-annulation of biphenyl amines with 1,6-enynes. This regioselective non-rollover cyclometallation was achieved through meticulous tuning of electronic factors of both the partners. This method is applicable to a wide range of protected o-arylanilines and enynes, and results in the regioselective preparation of benzo[f]isoindolyl derivatives in high yields with good diastereoselectivity (with respect to two types of stereogenic elements). Certain essential control experiments and kinetic isotope effect (KIE) studies were undertaken to elucidate the reaction mechanism, while subsequent transformations and a scale-up reaction were performed to substantiate the sturdiness of the transformation.

A scalable and environment-friendly one-pot two-component synthesis of chiral N-protected amino acid substituted 1,2,4-oxadiazoles from hydroxyl amidine and (S)-2-(2,2,2-trifluoroacetamido)propanoic 2,2,2-trifluoroacetic anhydride is described. This operationally simple methodology affords an efficient and convenient solution to synthesize chiral N-protected amino acids under catalyst-free conditions. All the synthesized compounds were screened for their in vitro antibacterial activity towards six human pathogenic bacterial species, among which, 4al exhibited a significant efficacy against Escherichia coli with the MIC value of 0.19 μg mL^-1.

Amphotericin B (AmB) has been clinically used for serious fungal infections for over 60 years. The drug is characterized by its specific recognition of ergosterol (Erg) in the fungal cell membrane. AmB and Erg form an ion-channel assembly, which is thought to play a major role in the antibiotic activity of AmB. The precise structure of the ion channel in fungal membranes still remains unelucidated. Recently, the structure of an AmB assembly formed in artificial lipid bilayers was determined using solid-state NMR and molecular dynamics simulations. The structure elucidation was made possible by using ¹³C- and ¹⁹F-labelled AmBs, which were efficiently synthesized using strategies and methods established in previous studies. This review focuses on the structure of the AmB ion channel, which accounts for the antibiotic activity. Additionally, the chemical syntheses of isotope-labelled AmB and Erg used for the structural studies are also reviewed. Solid-state NMR spectra of the labelled AmBs were recorded to measure the distances between labelled sites in the AmB-Erg assembly in lipid bilayers, revealing that the ion channel consisting of seven molecules of AmB spans the bilayer with a single molecule length. Extensive molecular dynamics simulations showed that the conductance of this AmB channel is comparable with those by single-channel recording. The simulations also demonstrated that Erg stabilizes the ion-channel assemblies more efficiently than human cholesterol. The atomic-level structure of the AmB channel in the artificial bilayer will help us to understand the mechanisms of the pharmacological actions and adverse effects of AmB.

A photooxidative C-C double bond cleavage of electron-deficient β-enaminocarbonyl compounds possessing a silyl group at the α-position to the nitrogen atom using methylene blue (MB) as the photosensitizer was explored. Photochemically generated ¹O₂ was added across the CC bond with the aid of a tethered silyl group to cleave it and form N-formylamines. This reaction protocol exhibited compatibility with numerous β-enaminocarbonyl substrates, including those with various N-alkyl, N-benzyl and N-aryl substituents.

It is commonly stated that alkyl groups exert an inductive electron-releasing effect when compared to hydrogen. This information has been given in numerous organic chemistry textbooks over the last 75 years. The evidence for this position is weak, and does not withstand scrutiny, and there is some evidence for the contrary position. We provide a significant body of computational data that clearly show that alkyl groups exert an inductive electron-withdrawing (-I) effect when compared to hydrogen. This revised position is not in conflict with experimental data, since alkyl group inductive effects are small and are likely to be masked by hyperconjugation/polarizability effects (particularly in charged species), and also by solvent effects.