10.1002/anie.201711535
The research focuses on the total synthesis of aurofusarin, a bis-naphthoquinone natural product, and an investigation into the atropisomeric stability of such compounds. The main content involves the development of an efficient annulation process that includes pyrone addition to a quinone and Dieckmann condensation to rapidly assemble a γ-naphthopyrone monomeric precursor. Dimerization was achieved through Pd(II)-catalyzed dehydrogenative coupling. The study also explores the configurational stability of aurofusarin's atropisomers using asymmetric nucleophilic epoxidation. Key reactants include methoxy benzoquinone, dienol ether, and various ligands for the Pd-catalyzed coupling. Analytical techniques used include X-ray crystallographic analysis for structural confirmation and chiral HPLC for assessing the stereochemistry and stability of the synthesized compounds. The experiments led to the discovery that the atropisomers of aurofusarin and its derivatives are not configurationally stable at ambient temperature, which has implications for the enantioselective synthesis of related natural products.
10.1134/S1070363211020320
The research focuses on the synthesis and reactions of cycloheptane dienone derivatives, which are compounds with aryl and heterocyclic substituents. The study aimed to introduce heterocyclic substituents into the structure of these dienone derivatives to create unequal electrophilic reaction centers, potentially expanding their practical applications. The experiments involved the condensation of monoenone derivatives with aldehydes under either alkaline or acidic catalysis to synthesize 7-arylmethylidene-2-hetarylmethyledene cycloheptanones (I–IV). Reactants included various aryl and heterocyclic compounds such as phenyl, m-nitrophenyl, furyl, 5-nitrofuryl, and thienyl substituents. The analysis of the synthesized compounds was conducted using infrared (IR) spectroscopy to identify characteristic absorption bands of conjugated C=O and C=C bonds, and nuclear magnetic resonance (NMR) spectroscopy, both proton (1H) and carbon (13C), to determine the chemical shifts and confirm the structure and configuration of the compounds. The study also investigated the reactions of these dienone derivatives with hydrazine, leading to the formation of cyclohepta[c]pyrazolines, with the reaction conditions and outcomes varying based on the presence of nitro groups in the benzene or furan rings.
10.1016/S0040-4020(00)00397-5
The study focuses on the stereoselective synthesis and organoleptic properties of p-menthane lactones (7a-h), a class of compounds with significant interest to the perfume industry due to their exceptional odor intensity and typical coumarin-like note. The research corrects published data concerning these compounds and identifies 7a, 7b, and 7g as trace components in Italo Mitcham black peppermint oil (Mentha piperita). Various chemicals were used in the study, including (-)-isopulegol, (+)-neoisopulegol, m-chloroperbenzoic acid, lithium diisopropylamide (LDA), potassium permanganate, Raney nickel, and several others, serving as starting materials, reagents, and catalysts in the synthesis of the lactones. The purpose of these chemicals was to facilitate the synthesis of the p-menthane lactones, allowing for their characterization and evaluation of their sensory properties, which are crucial for their potential use in the perfume and flavoring industries.
10.1080/00397910801929465
The study presents a convenient approach to the synthesis of dialkyl 5-oxo-1,2-dihydro-5H-chromeno[4,3-b]pyridine-2,3-dicarboxylates, which are compounds considered privileged scaffolds in synthetic and pharmacological research due to their potential pharmacological activities. The researchers focused on the chemical behavior of enaminocarbaldehydes derived from the coumarin moiety under intramolecular Wittig reaction conditions. Key chemicals used in the study include triphenylphosphine, dimethyl or diethyl acetylenedicarboxylates, and various enaminoaldehydes (1a–g), which are readily available by treating 4-hydroxycoumarin with different amines and then formylated under Vilsmeier-Haack reaction conditions. These chemicals served the purpose of facilitating the synthesis of the target compounds in good to high yields, expanding the scope of synthetic methods for creating biologically active ingredients and fluorescent dyes.
10.1021/acs.joc.5b01713
The research focuses on the development of an efficient method for the synthesis of coumarin derivatives, which are valuable natural products with a range of biological and pharmacological activities. The study utilizes a rhodium (Rh)-catalyzed annulation strategy involving the reaction of phenolic acetates with acrylates, activated via C-H bond activation. The process employs [Rh2(OAc)4] as a catalyst, formic acid as a reducing agent, and NaOAc as a base to achieve high yields of coumarin derivatives with excellent regioselectivity. The researchers concluded that this method is particularly useful for electron-deficient phenolic substrates and offers a complementary approach to existing methods, which are generally applicable only to electron-rich substrates. The study demonstrates the diversity-oriented synthesis of bioactive coumarin derivatives in high yields and under mild conditions, with a wide range of substrate scope.
10.1021/jm300922h
The study investigates the development of coumarin-based inhibitors targeting the replicative DNA helicase enzymes of Bacillus anthracis and Staphylococcus aureus, aiming to address the growing issue of drug-resistant bacterial infections. The researchers synthesized and evaluated a series of optimized coumarin-based inhibitors, finding that compounds 20 and 22 exhibited the highest potency against the helicases of both bacteria, with IC50 values of 3 and 1 μM, respectively. These compounds also demonstrated potent antibacterial activity against multiple ciprofloxacin-resistant MRSA strains, with MIC values ranging between 0.5 and 4.2 μg/mL. The study highlights the importance of the carboxylic acid group attached to the 3-position of the coumarin core and the substituents at the 7-position in determining the potency of the inhibitors. The findings suggest that further optimization of these coumarin-based helicase inhibitors could lead to the development of a new class of antibacterial agents effective against drug-resistant pathogens.
10.1007/s00044-018-2185-x
The research focuses on the synthesis and evaluation of novel coumarin/piperazine hybrid compounds as potential inhibitors of acetylcholinesterase (AChE), an enzyme associated with Alzheimer's disease (AD). The study aimed to develop new compounds with enhanced inhibitory activity against AChE, which could serve as leads for the development of anti-AD drugs. A series of 21 coumarin/piperazine hybrids were synthesized and tested for their ability to inhibit both human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The synthesis involved the preparation of coumarin-3-carboxylic acid derivatives, their condensation with Boc-protected piperazine, and subsequent deprotection and alkylation steps to introduce various substituents. The inhibitory activities of the synthesized compounds were assessed using the Ellman's method, and the most promising candidates were further subjected to kinetic assays and molecular docking studies to elucidate their mechanism of action and binding affinity at the active site of AChE. Additionally, the cytotoxicity of selected compounds was evaluated against the SH-SY5Y neuroblastoma cell line. The experiments utilized various analytical techniques, including NMR, MS, and elemental analysis, to characterize the synthesized compounds and assess their purity. The study identified compounds 4d and 4t as potent hAChE inhibitors with IC50 values of 2.42 and 9.89 μM, respectively, and compound 4t showed the highest selectivity for hAChE over hBChE.
10.1002/anie.201805203
The study presents a novel ring transposition process for synthesizing highly substituted 2-naphthols and BINOLs using lithium bases, specifically lithium diethylamide (LiNEt2) and lithium diisopropylamide (LDA). The process involves the conversion of readily available coumarins into 2-naphthols through a series of reactions where lithium bases act as both nucleophiles and bases. Initially, the lithium bases facilitate the ring opening of coumarins to form Z-cinnamamides, which serve as in situ directing groups. These Z-cinnamamides, with their conformational freedom, undergo a directed remote metalation and ring closure reaction, yielding aryl 2-naphthols in good to excellent yields. The study also provides mechanistic insights into the remote lateral metalation step, emphasizing the necessity of Z-cinnamamide for the reaction's success. Furthermore, the methodology is applied to the synthesis of highly substituted 3,3’-diaryl BINOL ligands, which are important in enantioselective synthesis and molecular recognition. The purpose of these chemicals is to demonstrate a new synthetic strategy that can efficiently produce complex molecular structures with potential applications in natural products, dyes, pigments, and as ligands and catalysts in asymmetric synthesis.
10.1007/s10600-007-0183-1
The study primarily focuses on the synthesis of 4-aminomethyl analogs of the natural coumarin daphnetin. The researchers investigated the reaction of 4-chloromethylcoumarins with aliphatic and aromatic amines to develop new bioactive coumarins with improved bioavailability, which are important in medical practice due to their broad spectrum of biological activity. The purpose of using these chemicals was to introduce a basic tertiary N atom and a free N–H group into the coumarin structure, which can enhance the bioavailability of the compounds. The study involved the preparation of starting 4-chloromethylcoumarins through Pechmann condensation and the subsequent alkylation of primary and secondary amines by these substituted 4-chloromethylcoumarins. The synthesized 4-aminomethyl coumarin derivatives were characterized by their physical properties and spectroscopic data, indicating their potential as new pharmacological agents.
10.1016/0040-4020(96)00480-2
The research focused on the cyclization of o-hydroxyphenyl ethynyl ketones, aiming to develop efficient synthetic methods for the construction of 2-substituted pyranones, which possess significant biological activities. The study was conducted from both theoretical and experimental standpoints, utilizing ab initio calculations at the HF/6-31G+ level to understand the cyclization process. The researchers generated phenoxide ions in situ under aprotic conditions through the desilylation of o-silyloxyphenyl ethynyl ketones with spray-dried potassium fluoride and 18-crown-6 in anhydrous DMF. This approach led to the smooth cyclization of various o-hydroxyphenyl ethynyl ketones, producing benzopyranone derivatives with high selectivity. The presence of a small amount of proton donor was found to be essential for the high 6-endo-digonal selectivity, and the study concluded that both 6-endo-digonal and 5-exo-digonal cyclizations are reversible in aprotic media, with the irreversible protonation of the resulting vinyl anion being critical for product formation.
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