Organic & Biomolecular Chemistry最新文献

The in situ generated aza-π-allylpalladium species, formed via the palladium-catalyzed decarboxylation of vinyloxazolidine-2,4-diones, were successfully used for the divergent reaction with 2-alkynylphenols and 2-alkynylanilines. Using Pd₂(dba)₃·CHCl₃ as the catalyst and Cu(OTf)₂ as the additive, a range of 2,3-disubstituted benzofurans and indoles were obtained in moderate to excellent yields. However, when PPh₃ ligand was added, a series of γ-O/N-substituted α,β-unsaturated amides were obtained in acceptable yields. This reaction demonstrates that vinyloxazolidine-2,4-diones are capable of undergoing palladium-catalyzed decarboxylative allylic functionalization with carbon, oxygen, and nitrogen nucleophiles.

Among the various heterocyclic organoselenium compounds, a new class of benzoselenazoles has received great attention due to their chemical properties and biological applications. The ever-growing interest in the five-membered benzoselenazole heterocycles amongst chemists has made commendable impact. These heterocycles are a prominent class of organic molecules that have emerged as potential therapeutic agents for the treatment of a wide range of diseases. Substantial progress has been made in elucidating the complex chemical properties of these heterocycles. Moreover, they have garnered significant importance in a wide range of biological applications. However, despite their biological activities, research on benzoselenazoles remains relatively limited, emphasising the need for further exploration in this area. Hence, considering the importance of benzoselenazoles, this comprehensive review compiles various synthetic procedures, highlighting the recent advances in their synthesis that have been disclosed in the literature. This review would offer chemists an array of information that will assist them in the development of more affordable and effective synthesis processes for benzoselenazoles. Therefore, it is believed that this review would provide relevant context on these achievements and will inspire synthetic organic chemists to use these effective technologies of such heterocycles for the future treatment of diseases caused by oxidative stress. The biological and pharmacological properties of these organoselenium heterocycles, which include their antioxidant, antitumor, and antibacterial activities and their application in Alzheimer's disease treatment and as pancreatic lipase inhibitors, are thoroughly summarized. Finally, this review provides some perspectives on the challenges and future directions in the development of benzoselenazoles as heterocyclic organoselenium compounds.

An unexpected cascade of N-acylation/intramolecular [4 + 2] cycloaddition/decarboxylation/isoxazole ring-opening reactions is observed in the course of the interaction between 3-(isoxazol-3-yl)allylamines and maleic or trifluoromethylmaleic anhydrides. This four-step sequence begins with the initial N-acylation of allylamines by the anhydride, followed by an intramolecular Diels-Alder reaction, which is accompanied by spontaneous decarboxylation, and ends with the opening of the isoxazole ring. As a result, an original approach to a pyrrolo[3,4-c]pyridine core was discovered. A test series of pyrrolo[3,4-c]pyridin-3-ones was investigated for anti-inflammatory activity and cytotoxicity, including the ability to inhibit NLRP3 inflammasome activation.

Herein, we report for the first time an additive- and catalyst-free dehydrogenative multicomponent reaction of arylglyoxal, malononitrile, and indoles for the one-pot synthesis of indole-linked β-cyano-enones in DMF medium. The reaction was performed at 100 °C in DMF, forming one C-C single bond and one CC double bond in a single-flask. Furthermore, we developed an efficient method for the synthesis of indolyl-2-pyrrolones having a hydroxyl group-containing chiral carbon center from the β-cyano-enones using trifluoroacetic acid and water as reaction medium. The β-cyano-enones were also further transformed into indolyl-1,2-diketones via a base-mediated reaction, which yielded indolyl quinoxalines upon reaction with o-phenylenediamine (OPD).

Indole scaffolds, which are important structural motifs in organic chemistry, have garnered sustained interest due to their prevalence in pharmaceuticals, agrochemicals, and natural products. This study establishes a novel umpolung activation strategy for γ-position functionalization of electron-poor alkenyl sulfoxides, generating allylidenesulfonium intermediates that are subsequently trapped by indoles, achieving the synthesis of 3-functionalized indoles. Further transformations and plausible mechanism were investigated.

C-Glycosides belong to a class of bioactive compounds biosynthesized by C-glycosyltransferases, also known as C-GTs. Despite their practical significance, C-GTs have scarcely been studied due to the limited availability of their crystal structures. In this study, we applied molecular dynamics (MD) simulations and density functional theory (DFT) calculations to investigate Glycyrrhiza glabra C-GT (GgCGT), focusing on the impact of protonation states of two histidine residues and specific mutations on enzyme-substrate configurations. We explored nine native ternary models, considering all possible combinations of protonation states for the His351/His373 pair, which we proposed as fundamental for catalysis. We also included four different mutants designed to assess the role of residues found to be essential for catalytic activity through mutagenesis experiments: His12Ala, His12Lys, His12Lysn and Asp375Ala. MD simulations revealed that only two models (M1 and M3) satisfied the criteria for catalytic competence, where the protonation states of His351 and His373 significantly influenced the relative position between donor and acceptor substrates, as well as the acceptor substrate conformation, adopting extended and packed states. DFT calculations confirmed that these conformations impact the electron density distribution, influencing substrate reactivity. Mutant simulations further supported the experimental data: His12Ala, His12Lys, and Asp375Ala mutants failed to meet the catalytic distance criteria, leading us to infer that these mutations prevented the formation of a reactive enzyme-substrate complex. Conversely, the His12Lysn mutant partially meets the criteria, which could help to explain the catalytic activity of this mutant. These findings provide the first molecular interpretation of the role of key residues in substrate binding and catalysis, which are essential for understanding catalytic activity. Furthermore, they offer new structural insights into residues such as His351/His373, which are often overlooked in GT modeling despite their potential to modulate the Michaelis complex. We hope that these findings will contribute to the rational engineering of more efficient C-GTs for biotechnological applications.

A Ni-catalyzed highly regioselective carboborylation bifunctionalization of allenes was developed, and a series of α-substituted-γ-boro-δ-enoates were generated in good to high yields. This reaction has the advantages of mild reaction conditions, a wide substrate scope and good late-stage modification applications, providing a new strategy for the synthesis of configurationally defined trisubstituted vinyl boron compounds.

The supramolecular assembly of amyloid-β into soluble oligomers is critical Alzheimer's disease (AD) progression. Soluble Aβ oligomers have emerged as neurotoxic species involved in AD progression and some Aβ oligomers are thought to be composed of β-hairpins. In this work, we report the X-ray crystallographic and solution-phase assembly of a macrocyclic β-hairpin peptide that mimics a β-hairpin formed by Aβ_16-36. In the crystal lattice, the peptide assembles into a symmetric hexamer composed of two identical triangular trimers. In aqueous solution, the peptide assembles to form an asymmetric hexamer. ¹H NMR, TOCSY, and ¹H,¹⁵N HSQC experiments establish that the asymmetric hexamer contains two different species, A and B. ¹⁵N-edited NOESY reveals that species A is a cylindrin-like trimer and species B is a triangular trimer that collectively constitute the asymmetric hexamer. Diffusion-ordered NMR spectroscopy (DOSY) suggests that two asymmetric hexamers further assemble to form a dodecamer. NMR-guided molecular mechanics and molecular dynamics studies provide a model for the asymmetric hexamer and suggest how two asymmetric hexamers can form a dodecamer. Solution-phase NMR studies of analogues show that intermolecular hydrogen bonding and the formation of a hydrophobic core help stabilize the asymmetric hexamer. These NMR and crystallographic studies illustrate how an Aβ β-hairpin peptide can assemble to form different well-defined oligomers in the crystal state and in aqueous solution, providing a deeper understanding of the heterogeneity of Aβ oligomers and new structural models of Aβ oligomers composed of Aβ β-hairpins.

A novel visible-light-driven method for the synthesis of 2,3-disubstituted quinazolinones has been developed, employing copper(II) as a catalyst in a sequential Ullmann N-arylation and C-H oxidative amidation process. This methodology utilizes o-iodo-N-substituted benzamides and benzylamines as substrates, with molecular oxygen sourced from ambient air functioning as the oxidant. The reaction is conducted under mild conditions, utilizing cost-effective copper(II) chloride as the catalytic agent and Eosin Y as a photosensitizer, facilitated by blue LED irradiation. A broad compatibility with various substrates is demonstrated, yielding products in the range of 30% to 84%. Additionally, mechanistic studies elucidate a single-electron transfer pathway that incorporates aryl radical intermediates. This research presents a sustainable and efficient strategy for the synthesis of quinazolinones, with considerable synthetic and mechanistic implications.

This review summarizes the methodologies for the selective functionalization of the B(3,6) vertices of o-carboranes, including the deboration-capitation reaction, the coupling reaction of B-X (X = I, Br) bonds, reactions of 1,3-dehydro-o-carborane and [3-N₂-o-C₂B₁₀H₁₁][BF₄] as well as transition-metal-catalyzed B-H activation. These works offer a versatile toolbox for synthesizing B(3,6)-substituted o-carborane derivatives and will promote their applications in material science, pharmaceutical chemistry, and related disciplines.