Search Results (86)

In this work, we described the synthesis of 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate by reacting 5-bromofuroic acid with methylparaben in the incorporation of DCC/DMAP (Steglich esterification) as coupling agents. Later on, we subsequently synthesized a series of 4-(methoxycarbonyl)phenyl 5-aryl furan-2-carboxylates (5a–5e) through Suzuki coupling catalyzed by palladium (0) between 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate (3) with several substituted arylated and heteroaryl boronic acids (4). DFT calculations were computed to elucidate electronic structural features of synthesized molecules (5a–5e) and to validate these findings by correlating with theoretical and experimental spectroscopic analysis. Furthermore, geometrical optimization, thermodynamic features, as FMO orbitals, MESP maps, NLO behavior and reactivity descriptors, were also determined from the PBE0 D3BJ/def2-TZVP/SMD_1,4-dioxane theory level to confirm the structural features of synthesized molecules. Full article

We report on the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide 5, evaluated for potential therapeutic applications. The compound was tested for its antioxidant and antimicrobial properties, demonstrating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide’s potential in biomedically relevant conditions that involve DNA modulation. Molecular docking and CD spectra deconvolution provided additional insights into the binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide’s lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at the ωB97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an antioxidant, through FMOs, MEP analysis, and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections. Full article

Background/Objective: Oligodeoxynucleotides (ODNs) containing base-labile modifications such as N4-acetyldeoxycytidine (4acC), N6-acetyladenosine (6acA), N2-acetylguanosine (2acG), and N4-methyoxycarbonyldeoxycytidine (4mcC) are highly challenging to synthesize because standard ODN synthesis methods require deprotection and cleavage under strongly basic and nucleophilic conditions, and there is a lack of ideal alternative methods to solve the problem. The objective of this work is to explore the capability of the recently developed 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) method for the incorporation of multiple 4acC modifications into a single ODN molecule and the feasibility of using the method for the incorporation of the 6acA, 2acG and 4mcC modifications into ODNs. Methods: The sensitive ODNs were synthesized on an automated solid phase synthesizer using the Dmoc group as the linker and the methyl Dmoc (meDmoc) group for the protection of the exo-amino groups of nucleobases. Deprotection and cleavage were achieved under non-nucleophilic and weakly basic conditions. Results: The 4acC, 6acA, 2acG, and 4mcC were all found to be stable under the mild ODN deprotection and cleavage conditions. Up to four 4acC modifications were able to be incorporated into a single 19-mer ODN molecule. ODNs containing the 6acA, 2acG, and 4mcC modifications were also successfully synthesized. The ODNs were characterized using RP HPLC, capillary electrophoresis, gel electrophoresis and MALDI MS. Conclusions: Among the modified nucleotides, 4acC has been found in nature and proven beneficial to DNA duplex stability. A method for the synthesis of ODNs containing multiple 4acC modifications is expected to find applications in biological studies involving 4acC. Although 6acA, 2acG, and 4mcC have not been found in nature, a synthetic route to ODNs containing them is expected to facilitate projects aimed at studying their biophysical properties as well as their potential for antisense, RNAi, CRISPR, and mRNA therapeutic applications. Full article

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI₅₀ 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI₅₀ concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer. Full article

Hypericum perforatum L. (St John’s wort) has been widely studied and used for antidepressant treatment, as well as, rarely, featuring in studies on its chemical composition for Parkinson’s disease (PD) treatment. Five new nor-prenylated acylphloroglucinols with a cyclohexanone core, norperforatums A–E (1–5), together with four known analogs [(2R,3R,4S,6R)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxopropyl)-3-(4-methyl-3-pentenyl)cyclohexanone (6), hyperscabrin B (7), (2R,3R,4S,6R)-6-methoxycarbonyl-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxopropyl)-3-(4-methyl-3-pentenyl)cyclohexanone (8), and hyperscabin K (9)], were isolated from the aerial parts of H. perforatum. The structures and absolute configurations of the new compounds were characterized by multiple spectroscopic means, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet visible absorption spectroscopy (UV), infrared spectroscopy (IR), calculated electronic circular dichroism (ECD) data, and X-ray signal crystal diffraction. In addition, the efficacy of these isolations was evaluated against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in zebrafish larvae. Compound 9 had the best therapeutic effect, by significantly increasing the total distance traveled and the mean speed of movement in PD dyskinesia zebrafish larvae. Moreover, it enhanced superoxide dismutase (SOD) activity and inhibited reactive oxygen species (ROS) production in a dose-dependent manner. These results suggest that compound 9 may have ameliorative effects on PD symptoms by inhibiting oxidative stress. This study provides new insights into the treatment of H. perforatum for PD. Full article

tert-Butyl hypochlorite was employed as a versatile reagent for chlorooxidation of indoles, chlorination of 2-oxindoles, and decarboxylative chlorination of the indole-2-carboxylic acids. Four types of products including 2-chloro-3-oxindoles, 2,2-dichloro-3-oxindoles, 3,3-dichloro-2-oxindoles, and 2,3-dichloroindoles could be selectively obtained in moderate to excellent yields by switching the substrates. Various synthetically useful functional groups, such as halogen atoms, cyano, nitro, and methoxycarbonyl groups, remain intact during the reactions. Notable features of the approach include the universality of the starting materials, the mild reaction conditions, and the experimental simplicity. Full article

The alkoxycarbonylation of styrene by palladium chloride is studied employing the density functional theory (DFT). Initially, [PdCl₃]^– reacts with methanol to form the methoxy-bound intermediate, which undergoes β-hydride elimination to form the key intermediate [PdCl₂H]^–. Then, a 1,2-insertion reaction to styrene takes place to form linear and branched alkyl coordinated with the Pd^II. Then, CO coordination followed by a 1,1-insertion reaction leads to the formation of acyl intermediate. Next, the methanolysis leads to the formation of esters. Previous reports with other catalysts suggested the intermolecular/intramolecular transition state (TS) formation with a high activation barrier, and this step was the bottleneck. To the best of our knowledge, this is the first time we have considered a two-step mechanism for the alcoholysis of the ester formation mechanism. After coordination with the metal, the methanol undergoes oxidative addition to form the Pd^IV square pyramidal intermediate, followed by reductive elimination to form the ester with regeneration of the metal hydride active intermediate. Deeper insight into the nature of bonding at the TSs is obtained through energy decomposition with natural orbital for chemical valence (EDA-NOCV) and quantum theory of atoms in molecules (QTAIM). Full article

FmocFF (9-fluorenyl methoxycarbonyl-phenylalanine) is an extensively studied low-molecular-weight hydrogel. Although there have been numerous studies on FmocFF hydrogel, its potential to form organogels has not been well explored. In this work, we systematically explore the organogels of FmocFF in a wide range of organic solvents. FmocFF is found to be a robust organogeltor, and the subsequent organogels exhibit diverse gelmorphic behavior exhibiting various degrees of crystallinity and morphology depending on the solvent used. The mechanical strength of the organogels is evaluated using rheology. A novel technique, in situ SHG microscopy, is introduced to study the gel structure in its native state. In addition to the solvent–solute interactions that are typically used to predict gelmorphic behavior, we observed indications that the degree of crystallinity also plays a significant role in determining the mechanical properties and structure of FmocFF organogels. Full article

The [PdCl₂(Xantphos)] complex, in comparison with several [PdCl₂(P–P)] complexes having different diphosphine chelating ligands (P–P), is very active as a catalyst for the carbonylation of iodobenzene to methyl benzoate. The run conditions and the influence of several cocatalysts have been also studied to further improve the catalytic activity. The optimization of the catalytic system allowed to obtain TOFs of ca. 260,000 h⁻¹. The addition of some additives able to reduce the possible catalyst deactivation allowed to increase the TOF of ca. 15%. The best positive results were obtained by adding reducing agents such as ferrocene, which leads to a TOF higher than 300,000 h⁻¹. Full article

Tyrosol and hydroxytyrosol are powerful phenolic antioxidants occurring in olive oil and in by-products from olive processing. Due to their high polarity, esterification or other lipophilization is necessary to make them compatible with lipid matrices. Hydroxytyrosol methyl carbonate is a more effective antioxidant than dibutylhydroxytoluene or α-tocopherol and together with tyrosol methyl carbonate exerts interesting pharmacological properties. The purpose of this work was the enzymatic preparation of alkyl carbonates of tyrosol and hydroxytyrosol. A set of 17 hydrolases was tested in the catalysis of tyrosol methoxycarbonylation in neat dimethyl carbonate to find an economically feasible alternative to the recently reported synthesis of methyl carbonates catalyzed by Novozym 435. Novozym 435 was, however, found to be the best performing catalyst, while Novozym 735, pig pancreatic lipase, lipase F-AK and Lipex 100T exhibited limited reactivity. No enzyme accepted 1,2-propylene carbonate as the acylation donor. Under optimized reaction conditions, Novozym 435 was used in the batch preparation of tyrosol methyl carbonate and hydroxytyrosol methyl carbonate in quantitative yields. The enzymatic methoxycarbonylation of tyrosol and hydroxytyrosol can also be used as a method for their selective protection in enzymatic syntheses of phenylethanoid glycosides catalyzed with enzymes comprising high levels of acetyl esterase side activity. Full article

A synthesis of benzo[d]oxazoles by an N-deprotonation–O-S_NAr cyclization sequence from anilide precursors is reported. Anilides derived from 2-fluorobenzaldehydes, activated toward S_NAr ring closure by C5 electron-withdrawing groups, were prepared and subjected to deprotonation–cyclization using 2 equiv. of K₂CO₃ in anhydrous DMF. Following deprotonation at nitrogen, the delocalized anion cyclized from the amide oxygen to give high yields of benzo[d]oxazoles. The temperature required for the cyclization of benzanilides correlated with the potency of the C5 activating group on the S_NAr acceptor ring with nitro (most potent) reacting at 90 °C (1 h), cyano reacting at 115 °C (1 h), methoxycarbonyl reacting at 120 °C (2 h), and trifluoromethyl (least potent) reacting at 130 °C (3 h). Acetanilides were more difficult to cyclize but generally required 4–6 h at these same temperatures for completion. Product purification was accomplished by recrystallization or chromatography. Full article

This study explores the potential of copper-doped nickel oxide (Cu:NiO) as a hole transport layer (HTL) in flexible photovoltaic (PV) devices using a combined first-principles and finite element analysis approach. Density functional theory (DFT) calculations reveal that Cu doping introduces additional states in the valence band of NiO, leading to enhanced charge transport. Notably, Cu:NiO exhibits a direct band gap (reduced from 3.04 eV in NiO to 1.65 eV in the stable supercell structure), facilitating the efficient hole transfer from the active layer. Furthermore, the Fermi level shifts towards the valence band in Cu:NiO, promoting hole mobility. This translates to an improved photovoltaic performance, with Cu:NiO-based HTLs achieving ~18% and ~9% power conversion efficiencies (PCEs) in perovskite and poly 3-hexylthiophene: 1-3-methoxycarbonyl propyl-1-phenyl 6,6 C 61 butyric acid methyl ester (P3HT:PCBM) polymer solar cells, respectively. Finally, a finite element analysis demonstrates the potential of these composite HTLs with Poly 3,4-ethylene dioxythiophene)—polystyrene sulfonate (PEDOT:PSS) in flexible electronics design and the optimization of printing processes. Overall, this work highlights Cu:NiO as a promising candidate for high-performance and flexible organic–inorganic photovoltaic cells. Full article

Zanthoxylum simulans Hance, commonly known as Sichuan pepper, is a well-known medicinal plant recognized for its potential as a source of bioactive specialized metabolites. As part of our interest in natural antifungal compounds, the present study describes the discovery of an unreported N-alcoxycarbonylbenzo[c]phenanthridinium salt, N-methoxycarbonyl-9,12-dimethoxy-norchelerythrine 1 (a type-III benzo[c]phenanthridine), isolated from Z. simulans seedlings, which were propagated under controlled greenhouse conditions. Six-month seedlings were harvested and subjected to cold acid–base extraction. Chromatographic techniques achieved the isolation of 1 from raw alkaloid extract. The structural elucidation of 1 was accomplished through comprehensive spectroscopic analysis, including nuclear magnetic resonance and high-resolution mass spectrometry. Fusarium oxysporum, a fungal pathogen responsible for substantial agricultural losses, was exposed to different concentrations of the novel compound, exhibiting potent antifungal efficacy (IC₅₀ < 3 µM) and fungicide effects. These findings highlight the potential of benzophenanthridines as antifungal leads and underscore the importance of exploring natural products for agricultural applications. Full article

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing. Full article

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates. Full article