Good Substrate Research Articles

Phosphinothio(seleno)ation of alkynes/olefins and application on the late-stage functionalization of natural products

Non-metallic catalysis has been known as a remarkable development strategy for hydrofunctionalization of unsaturated hydrocarbons. Herein, we report a unique chemically active method of BF3·OEt2 promoted multi-component, highly regioselective, and chemoselective hydrothio(seleo)phosphonylation of unsaturated hydrocarbons, which exhibits high yield and good substrate universality. The reaction mechanism was further elucidated to be Markovnikov addition by controlling experiments, 31P and 19F NMR spectra tracking experiments, X-ray diffraction analysis, and DFT calculations. Furthermore, the gram-scale attempt and the application of the reaction on the derivatization of natural products have been successfully conducted, leading to the discovery of 3as with potential anti-Parkinson's disease (PD) activities at 1 μM. This streamlined and efficient methodology has established a new platform for non-metallic Lewis acids-promoted hydrofunctionalization of unsaturated hydrocarbons and its application on new drug research.

Insights into transglutaminase on structural and rheological properties of gels from adzuki bean protein pretreated by electric fields

The demand for protein is increasing as the global population continues to grow. The plant protein has been favored and plant-based food has become a research hotspot for healthy diet, environmental protection, animal ethics and other issues. Adzuki bean protein (ABP) is a quality source with complete amino acids, abundant essential amino acids and beanless flavour. ABP is rich in glutamine and lysine which are good substrates for transaminase (TGase) induced gelation. The pulsed electric field (PEF), alternating current EF (ACEF), direct current EF (DCEF) were applied to pretreat ABP aiming at improving the efficacy of TGase induced crosslinking. The results showed that the TGase decreased the free amino amount significantly and increased the molecular weight of ABP. The EF pretreatments significantly influenced the secondary and tertiary structures of ABP with a decrease in β-sheets, increase in random coils, β-turns, and α-helices, also decrease in fluorescence intensity with blueshift. The content of disulfide bond increased with the decrease of free sulfhydryl groups. The ionic bonds decreased and hydrophobic actions surpassed significantly hydrogen bonds. The hydrophobicity increased. The electric field intensity corresponded to variation of microstructure, texture and rheological behaviour of the ABP gel according to the type of the EF.

Asymmetric Formal [5 + 2] Annulation of 3-Hydroxyquinolinones and Vinylethylene Carbonates through Pd/Cu Tandem Catalysis.

The asymmetric [5 + 2] cycloaddition of VECs remains to be comparatively rare. Herein, we reported an enantioselective formal [5 + 2] annulation of 3-hydroxyquinolinones and vinylethylene carbonates (VECs) through Pd- and Cu-catalyzed tandem allylation/asymmetric [1,3]-rearrangement/hemiketalization sequences. The strategy exhibits good substrate tolerance, affording a wide range of tricyclic quinolinones bearing two adjacent quaternary stereocenters in moderate to good yields with excellent enantioselectivities.

Photo‐Induced Difluoroethylation or Monofluoromethyl Sulfonylation of 2‐Amino Aryl Ethynes to Access Diverse Seven‐Membered N‐Heterocycles

AbstractA photo‐induced two/three‐component radical difluoroethylation or monofluoromethyl sulfonylation of 2‐amino aryl ethynes was smoothly finished, which gave a series of difluoroethyl or monofluoromethyl sulfonyl seven‐membered N‐heterocycles. The two radical systems featured simple/mild reaction conditions, good substrate scopes, and excellent E/Z selectivity. In addition, various radical intermediates were successfully detected by HRMS to explore the reaction process. Single‐crystal X‐ray diffraction and scaled‐up experiments examined the product scaffold and application of this cyclization system.

N, P co-doped porous biochar supported electron deficient Niδ+ for domino reductive amination and amidation of levulinic acid with nitroarenes to N-substituted pyrrolidones using methyl formate

The synthesis of N-substituted pyrrolidones starting from biomass-derived levulinic acid (LA) and nitroarenes is a highly attractive route for LA valorization, but still faces challenges. Herein, we report an electron deficient Niδ+ catalyst (Ni2P/NPCB-600) prepared by doping N and P into coffee biochar using a one-pot carbonization method. Ni2P/NPCB-600 shows outperform catalytic performance compared with the corresponding metallic Ni catalysts (Ni/CB-600 and Ni/NPCB-600) in the domino reductive amination and amidation of LA with nitroarenes. Characterization and controlled experiments demonstrate that the high catalytic activity and selectivity of Ni2P/NPCB-600 are mainly attributed to the formation of electron deficient Niδ+ (Ni2δ+-Pδ-), which could promote the decomposition of methyl formate, and the adsorption and activation of C=O bonds in LA during the domino reactions. Furthermore, Ni2P/NPCB-600 also shows good substrate scope, various N-substituted pyrrolidones can be directly synthesized from LA and different nitroarenes with good to excellent yields (87.5–99 %). This study provides a potential pathway for efficiently producing N-substituted pyrrolidones by adjusting the electron density of Ni.

Regio- and Stereoselective Construction of 1,3,5-Triaroylcyclohexanes via KOtBu-Mediated Cyclotrimerization of Aryl Vinyl Ketones.

Herein, we disclose a simple one-pot method for an efficient regio- and stereoselective synthesis of 1,3,5-triaroylcyclohexanes from aryl vinyl ketones using potassium tert-butoxide. The developed protocol allows the construction of various symmetrically substituted cyclohexanes in good to excellent yields. The major product 2 also can be converted to the product 3 (all equatorial) conveniently by acid catalysis. This protocol features a good substrate scope and functional group compatibility.

A Novel 2-Methylimidazole Promoted Oxyacyloxylation of α-Hydroxy Ketones and Anhydrides: An Easy Access to α-Acyloxy Ketones

An efficient and operationally simple method for the synthesis of α-acyloxy ketones through the readily available 2-methylimidazole-promoted reaction of α-hydroxy ketones and anhydrides is developed. In the reaction, the anhydrides act as both a substrate and a solvent. The new method features good substrate tolerance, mild reaction conditions, readily accessible starting materials, and excellent yields, providing facile and green access to the targets. Importantly, the reaction also avoids the use of reagents with pungent odors, such as pyridine, in traditional esterification, which may promote the development of organocatalysis using nitrogen-containing heterocyclic compounds as catalysts.

Reductive Coupling of N-Heteroarenes and 1,2-Dicarbonyls for Direct Access to γ-Amino Acids, Esters, and Ketones Using a Heterogeneous Single-Atom Iridium Catalyst.

Despite their significant importance, the challenges in direct and diverse synthesis of N-heterocyclic γ-amino acids/esters/ketones hamper exploration of their applications. Herein, by developing a multifunctional heterogeneous iridium single-atom catalyst composed of silica-confined iridium species and a boron-doped ZrO2 support (Ir-SAs@B-ZrO2/SiO2), we describe its utility in establishing a new reductive coupling reaction of N-heteroarenes and 1,2-dicarbonyls for selective and diverse construction of the as-described compounds in a straightforward manner. The striking features, including good substrate and functionality tolerance, high step and atom economy, exceptional catalyst reusability, and diversified product post-transformations, highlight the practicality of the developed chemistry. Mechanistic studies reveal that the synergy between the active Ir sites and acidic support favors a chemoselective reduction of the more inert N-heteroarenes and affords requisite enamine intermediates. In this work, the concept on precise transformation of reductive intermediates will open a door to further develop useful tandem reactions by rational catalyst design.

N-heterocyclic carbene switchable radical or benzyne meditated arylation of thiols using DMF/KOtBu

A mild, metal and photoredox-free direct arylation of alkyl and aryl thiols with aryl iodides using a DMF/KOtBu system has been developed. In the absence of an N-heterocyclic carbene (NHC) additive, the reaction proceeds via a benzyne intermediate and was suitable for the substitution of thiols with phenyl, while the presence of an NHC or phenanthroline derivative improves regioselectivity for the reaction of substituted aryl iodides via a radical pathway. This protocol features inexpensive materials and good substrate scope, and could be useful in the arylation of aryl and alkyl thiols.

The refined CYP2B6-Template system for studies of its ligand metabolisms

The previously reported Template system for the prediction of human CYP2B6-mediated reactions (Drug Metab Pharmacokinet 26 309-330, 2011) has been refined with the introduction of ideas of allowable width, Trigger*-residue and the residue-initiated movement of ligands in the active site. The refined system also includes ideas of bi-molecule binding on Template. With the use of these ideas in common with other Template systems for human CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, and CYP3A4, 360 reactions of 261 distinct chemicals reported as CYP2B6 ligands were examined in the refined system. From their placements on the refined Template and rules for interaction modes, verifications of good and poor substrates, regio- and stereo-selectivities, and inhibitory interaction became faithfully available for these ligands, in which all the chemicals tested in the previous study were included. From the comparison of substrate specificities of human CYP2B6 and rat CYP2B1, size differences of one of the enzyme residues, Shelf, were suggested as a cause of their distinct catalyses. The refined CYP2B6-Template system will thus offer more reliable estimations of this human CYP catalyses toward ligands of diverse structures, together with their deciphering information to lead to judgments of metabolisms.

Novel and reusable magnetic MOF nanocomposite coupled ionic liquid- promoted efficient chemical fixation of CO2 into α-alkylidene cyclic carbonates

Carbon dioxide as a C1 building block to synthesize α-alkylidene cyclic carbonates is an environmental and sustainable approach. In this work, we designed and synthesized a type of multifunctional magnetic MOF nanocomposite catalysts, which could realize the carboxylic cyclization of CO2 and propargylic alcohols into α-alkylidene cyclic carbonates under solvent-free conditions. Among all the prepared nanocomposites, the MnFe2O4@SiO2@Cu-MOF nanocomposite is the best in catalytic activity combined with the tetrabutylphosphonium acetate ([Bu4P]OAc) ionic liquid cocatalyst. The catalytic system MnFe2O4@SiO2@Cu-MOF/[Bu4P]OAc displayed excellent performance in catalyzing the carboxylic cyclization of CO2 and different propargylic alcohols, and a series of α-alkylidene cyclic carbonates were obtained in high to excellent yields (88 ∼ 98 %) under mild reaction conditions (0.2 MPa, 35 °C). In addition, the two-component catalytic system had high stability and reusability, and can be easily separated and reused up to six consecutive cycles without considerable decrease in catalytic activity. Moreover, using the ionic liquid [Bu4P]OAc as the cocatalyst, the nanocomposite had good substrate adaptability for the catalytic carboxylic cyclization, which opens interesting prospects for the development of new magnetic MOF nanocomposites as efficient heterogeneous catalysts for the chemical transformation of CO2 into value-added chemicals.

Design, Synthesis, Physicochemical Properties, and Biological Activity of Thymidine Compounds Attached to 5,8-Quinolinedione Derivatives as Potent DT-Diaphorase Substrates.

After heart disease, cancer is the second-leading cause of death worldwide. The most effective method of cancer treatment is target therapy. One of the potential goals of therapy could be DT-diaphorase, which reduces quinone moiety to hydroquinone, and reactive oxygen species are create as a byproduct. The obtaining of hybrid compounds containing the quinone moiety and other bioactive compounds leads to new derivatives which can activate DT-diaphorase. The aim of this research was the synthesis and characterization of new hybrids of 5,8-quinolinedione with thymidine derivatives. The analysis of the physicochemical properties shows a strong relationship between the structure and properties of the tested compounds. The enzymatic assay shows that hybrids are good substrates of NQO1 protein. The analysis of the structure-activity relationship shows that the localization of nitrogen atoms influences the enzymatic conversion rate. The analysis was supplemented by a molecular docking study. Comparing the results of the enzymatic assay and the molecular docking presents a strong correlation between the enzymatic conversion rate and the scoring value.

Targeting the Leloir Pathway with Galactose-Based Antimetabolites in Glioblastoma.

Glioblastoma (GBM) uses Glut3 and/or Glut14 and the Leloir pathway to catabolize D-Galactose (Gal). UDP-4-deoxy-4-fluorogalactose (UDP-4DFG) is a potent inhibitor of the two key enzymes, UDP-galactose-4-epimerase (GALE) and UDP-Glucose 6-dehydrogenase (UGDH), involved in Gal metabolism and in glycan synthesis. The Gal antimetabolite 4-deoxy-4-fluorogalactose (4DFG) is a good substrate for Glut3/Glut14 and acts as a potent glioma chemotherapeutic. Primary GBM cell cultures were used to examine toxicity and alterations in glycan composition via lectin binding in fixed cells and by Western blots. Toxicity/efficacy in vivo data was performed in mouse flank and intracranial models. The effect of 4DFG on D-glucose (Glc) metabolism in GBM cells was assessed by using 13C NMR-based tracer studies. 4DFG is moderately potent against GBM cells (IC50: 125-300 µM). GBM glycosylation is disrupted by 4DFG. Survival analysis in an intracranial mouse model showed that treatment with 4DFG (6 × 25 mg/kg of 4DFG, intravenously) improved outcomes by three-fold (p < 0.01). Metabolic flux analysis revealed that both glycolytic and mitochondrial metabolic fluxes of [U-13C]Glc were significantly decreased in the presence of 4DFG in GBM cells. A functional Gal-scavenging pathway in GBM allows Gal-based antimetabolites to act as chemotherapeutics. 4DFG is metabolized by GBM in vitro and in vivo, is lethal to GBM tumors, and is well tolerated in mice.

Photoredox Radical‐Polar Crossover Reaction of gem‐Difluoroalkenes: A Facile Access to Diverse Difluoroalkyl Sulfides

AbstractDifluoroalkyl sulfide (‐CF2S‐) moieties are an important class of skeletons in medicinal chemistry. Herein, a photoredox radical‐polar crossover reaction is reported for the three‐component thiofluorination, thiohydroxylation, thioalkoxylation, thioaminolation, and thiochlorination of gem‐difluoroalkenes towards diverse α‐functionalized difluoroalkyl sulfides. Such an approach features mild conditions, operational simplicity, and good substrate scope.

Solvent‐Free Synthesis of Carvone Oxime Ester and Carvone Oxime Sulfonic Esters

AbstractA ZnO‐mediated benzoylation between carvone oxime and acyl is reported, enabling access to diverse carvone oxime ester and carvone oxime sulfonic esters under solvent‐free conditions. The operationally simple procedure provides a novel method for the synthesis of oxime‐ester bonds with excellent chemo selectivity. This strategy provides a mild, direct, and green approach for synthesizing carvone oxime ester in moderate to excellent yields with good substrate tolerance. In addition, carvone oxime was synthesized under solvent‐free conditions.

Mechanochemical preparation and performance regulation mechanism of highly durable and multifunctional iron red nanocomposite pigments derived from natural mixed-dimensional palygorskite clay

Iron oxide red pigments are one of the most widely used inorganic red pigments around the world. It is always pursed to improve their physicochemical properties. Herein, a continuous mechanochemical method was employed to fabricate high-performance iron red nanocomposite pigments via anchoring α-Fe2O3 nanoparticles on the surface of natural mixed-dimensional palygorskite clay (MDPal). The mechanical force of twin-screw extrusion promoted the Si-OH groups of MDPal to coordinate with Fe3+ to form the precursor, while MDPal was activated with the residual H+ of the involved nitrate to accelerate the thermal diffusion of Al3+ into α-Fe2O3 crystal lattice, thus the nanocomposite pigments presented a bright yellowish-red color (L∗ ​= ​35.61, a∗ ​= ​33.10, b∗ ​= ​35.86, C∗ ​= ​48.80). Furthermore, the mixed-dimensional nanostructure of MDPal served as a good substrate for chemical bonding of α-Fe2O3 nanoparticles to improve the dispersion and environmental stability of iron red pigments. Due to the synergistic effect of each component and the excellent thermal and chemical stability, the obtained nanocomposite pigments exhibited excellent application prospect as functional inorganic pigments for anti-corrosion coating, overglaze ceramic and coloring and reinforcing of polypropylene, respectively. It provided a facile strategy for preparation of high-performance multifunctional iron red pigments based on MDPal.

Nucleoside Scaffolds and Carborane Clusters for Boron Neutron Capture Therapy: Developments and Future Perspective.

Nucleosides containing carboranes are one of the most important boron delivery agents for boron neutron capture therapy, BNCT, which are good substrates of hTK1. The development of several nucleosides containing carboranes at early stages led to the discovery of the first generation of 3CTAs by incorporating a hydrocarbon spacer between the thymidine scaffold and carborane cluster and attaching dihydroxylpropyl group on the second carbon (C2) atom of the carborane cluster (e.g., N5 and N5-2OH). Phosphorylation rate, tumor cellular uptake, and retention have been evaluated in parallel to change the length of the tether arm of spacers in these compounds. Many attempts were reported and discussed to overcome the disadvantage of the first generation of 3CTAs by a) incorporating modified spacers between thymidine and carborane clusters, such as ethyleneoxide, polyhydroxyl, triazole, and tetrazole units, b) attaching hydrophilic groups at C2 of the carborane cluster, c) transforming lipophilic closo-carboranes to hydrophilic nidocarborane. The previous modifications represented the second generation of 3CTAs to improve the hydrogen bond formation with the hTK1 active site. Moreover, amino acid prodrugs were developed to enhance biological and physicochemical properties. The structure-activity relationship (SAR) of carboranyl thymidine analogues led to the roadmap for the development of the 3rd generation of the 3CTAs for BNCT.

Ultrathin natural biotite crystals as a dielectric layer for van der Waals heterostructure applications

Biotite, an iron-rich mineral belonging to the trioctahedral mica group, is a naturally abundant layered material (LM) exhibiting attractive electronic properties for application in nanodevices. Biotite stands out as a non-degradable LM under ambient conditions, featuring high-quality basal cleavage-a significant advantage for van der Waals heterostructure (vdWH) applications. In this work, we present the micro-mechanical exfoliation of biotite down to monolayers (1Ls), yielding ultrathin flakes with large areas and atomically flat surfaces. To identify and characterize the mineral, we conducted a multi-elemental analysis of biotite using energy-dispersive spectroscopy mapping. Additionally, synchrotron x-ray fluorescence and infrared nano-spectroscopy were employed to probe its iron content and vibrational signature in few-layer form, respectively, with sensitivity to the layer number. We have also observed good morphological and structural stability in time (up to 12 months) and no important changes in their physical properties after thermal annealing processes in ultrathin biotite flakes. Conductive atomic force microscopy evaluated its electrical capacity, revealing an electrical breakdown strength of approximately 1 V nm-1. Finally, we explore the use of biotite as a substrate and encapsulating LM in vdWH applications. We have performed optical and magneto-optical measurements at low temperatures. We find that ultrathin biotite flakes work as a good substrate for 1L-MoSe2, comparable to hexagonal boron nitride flakes, but it induces a small change of the 1L-MoSe2g-factor values, most likely due to natural impurities on its crystal structure. Furthermore, our results show that biotite flakes are useful systems to protect sensitive LMs such as black phosphorus from degradation for up to 60 days in ambient air. Our study introduces biotite as a promising, cost-effective LM for the advancement of future ultrathin nanotechnologies.

Pelatihan pembuatan minuman probiotik fermentasi dari limbah kulit nanas (Ananas comosus L.) di Desa Seruawan

Pineapple skin is an ingredient that can be processed into a probiotic drink. The biggest component of pineapple peel waste besides water is carbohydrates. Pineapple skin can be a good substrate as a source of microbial growth. Pineapple skin can reach 47% of the total fruit and has a chemical composition of 87.80% water, 8.60% sugar and 1.35% reducing sugar. The potential chemical content of pineapple skin has encouraged many researchers to create fermented prebiotic drink products. The ingredients used in making pineapple peel fermented probiotic drinks include: pineapple fruit, fermented yeast, water, palm sugar, cinnamon and granulated sugar. This community service activity was carried out with the aim of educating the public about how to make pineapple peel prebiotic drinks for household scale. There is a need for training in making fermented prebiotic drinks from pineapple peel in local communities. This training will be carried out for the community in Seruawan village, Seram Island, Maluku.

Characterization of a Novel Acid-Stable Chitosanase from Lentinula edodes Suitable for Chitooligosaccharide Preparation

As high-value chitosan derivatives, chitooligosaccharides (COSs) with biodegradable, biocompatible, nontoxic, antimicrobial, and antioxidant activities have been widely applied in food-related fields. Chitosanases can hydrolyze chitosan to produce COSs. Herein, a chitosanase (LeCho1) from Lentinula edodes was successfully expressed in Escherichia coli and was then purified and characterized. LeCho1 had a low sequence identity with other chitosanases reported from the GH75 family. The recombinant protein showed a molecular mass of 27 kDa on SDS-PAGE. LeCho1 preferentially hydrolyzed chitosan with a high degree of deacetylation (DDA) and exhibited maximal activity (71.88 U/mg) towards 95% DDA chitosan at pH 3.0 and 50 °C. It possessed good stability at pH 2.0–6.0 and temperatures below 45 °C. Its hydrolytic activity was remarkably enhanced by the metal ion Mn2+ at 1 mM, while it was totally inhibited by 1 mM Fe3+ or 10 mM EDTA. Its Km and Vmax values were 0.04 μM and 76.81 μmol·min−1·mg−1, respectively, indicating good substrate affinity. LeCho1 degraded chitosan into COSs with degrees of polymerization (DPs) of 2–5, while it had no action on COSs with DPs of less than 5, revealing its endo-chitosanase activity. This study proved that chitosanase LeCho1 is a promising candidate in the industrial preparation of COSs due to its excellent properties.