Short Synthesis Research Articles

Urea-Promoted Neat Synthesis of Fused Dihydroisoquinolines and Disubstituted Pyridines: A Mechanistic Observation with Molecular-Sensing Studies.

An efficient and short synthesis of fused dihydroisoquinolines, diaryl substituted pyridine derivatives in good to high yields has been established by using an environmentally safe, solvent-metal-oxidant-free tandem approach. In this article, we discuss how the electrocyclic reaction is more pronounced in the solid phase in the presence of urea, whereas the typical aza-Michael addition is more prominent in presence of arylamine in the solution phase for 3-(2-formylcycloalkenyl)acrylic ester derivative substrates. The wide range of substrates and urea-promoted neat synthesis made our approach more significant in medical and also analytical science. Moreover, an isoquinoline alkaloid decumbenine B analogue has been synthesized by using our newly developed neat methodology. We have also investigated the photophysical properties of the synthesized fused dihydroisoquinoline derivatives. One of the synthesized molecules was used as a sensor for the selective detection of toxic picric acid. Therefore, the effective neat synthesis and molecular sensing applications of these compounds made our approach more exciting in the field of heterocyclic chemistry.

A rhodium-catalyzed C-H activation/cyclization approach toward the total syntheses of cassiarin C and 8-O-methylcassiarin A from a common intermediate.

Three short and efficient total syntheses of cassiarin C are reported, from a chromanone common key intermediate. A C-H activation strategy, under rhodium catalysis on its pivaloyl oxime, enabled the installation of the pyridine ring. Dehydrogenation of 8-O-methylcassiarin C afforded 8-O-methylcassiarin A. A kinetic experiment and DFT calculations of the intermediates helped to gain insight into the unusual site- and stereo-specific H/D exchange of cassiarin C in CD3OD.

Chemoenzymatic total synthesis of rotigotine via IRED-catalyzed reductive amination.

A short and chemoenzymatic synthesis of rotigotine using an IR-36-M5 mutant is reported. Focusing on the residues that directly contact the 2-tetralone moiety, we applied structure-guided semi-rational design to obtain a double-mutant F260W/M147Y, which showed a good isolated yield and S-stereoselectivity >99% toward 2-aminotetralin synthesis. Furthermore, the utility of this biocatalytic protocol was successfully demonstrated in the enantioselective synthesis of rotigotine via enzymatic reductive amination as the key step.

Facile protocol, metal-free, one-pot synthesis of 2-amino-4H-chromenes, benzimidazoles, and benzothiazoles via acidic ionic liquids based on pyridinium

In a one-pot tandem condensation reaction, three functional ionic liquids (ILs) derived from pyridinium were employed as green, reusable, and efficient catalysts for the synthesis of important medicinal chemistry derivatives such as 2-amino-4H-chromenes. Additionally, benzimidazoles and benzothiazoles were synthesized using these catalysts. The ILs were favored for their easy set-up, high yields, and short synthesis times for the desired products. Moreover, the ILs could be easily recovered and reuse multiple times without significant loss of catalytic activity. Characterization of the synthesized compound was achieved through FT-IR, 1H NMR, 13C NMR, TGA and melting point analysis. The compounds were prepared with good to excellent isolated yields under mild conditions, while the synthesis of benzimidazoles and benzothiazole derivatives was successful at both reflux and room temperature conditions. Finally, each class of compound was described along with its corresponding synthesis mechanism.

Influence of deposition conditions on performance of Ni3S2 as the bifunctional electrocatalyst in alkaline solutions by galvanostatic deposition

The electrodeposition method is a popular synthesis method due to its low cost, simplicity, and short synthesis time.

GAD plasma-assisted synthesis of ZnO nanoparticles and their photocatalytic activity

In this study we present an efficient method for synthesizing highly pure ZnO nanoparticles using a Gliding Arc Discharge (GAD) plasma system as a non-thermal plasma source. This approach offers distinct advantages over conventional techniques, including simplicity, a short synthesis time, utilization of readily available air as the source gas, and potential scalability, rendering it a promising alternative for sustainable ZnO nanoparticle production. The synthesized nanoparticles physicochemical properties were characterized using various techniques, such as scanning electron microscopy (SEM), energy dispersive x-ray analysis (EDAX), UV-visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). Furthermore, we evaluated the effectiveness of the synthesized ZnO nanoparticles for wastewater treatment by assessing their photocatalytic activity against methylene blue (MB), Brilliant Cresyl Blue (BCB), and Congo Red (CR) under UV light irradiation for 2 h and 30 min. The results confirmed the successful synthesis of highly pure ZnO nano-powder with an average size of 27.18 nm and a band gap energy of 3.28 eV in an exceptionally brief duration and through straightforward steps. Additionally, GAD plasma-assisted ZnO nanoparticles exhibited a significant dye removal rate, showcasing their potential as highly effective materials for photocatalytic wastewater treatment. This study contributes new insights into the application of GAD plasma for nanoparticle synthesis.

Synthesis of halogenated benzimidazolyl-C-nucleosides and their activity against Leishmania major and Leishmania tropica

Here we report the short synthesis of “reversed” halogenated C-nucleoside (benzimidazole) analogs.

Green synthesis of silver nanomaterials using Ganoderma Lucidum extract as reducing agent and stabilizer with ultrasonic assistance and application as an antibacterial agent

Synthesis of silver nanoparticles (AgNPs) using plant extracts extracted from Ganoderma lucidum in the buffer zone of Bach Ma National Park, Vietnam is a simple, convenient, economical, and environmentally friendly method. This study describes the biosynthesis of silver nanoparticles in both cases with and without ultrasonic assistance using Ganoderma lucidum extract as a reducing and protective agent. Transmission electron microscopy, scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy were used to characterize the as-synthesized AgNPs. Compared to the heating reflux method, the proposed ultrasonic wave assisted heating reflux method produced AgNPs had higher efficiency, smaller and more uniform particle size 6.08 ± 1.80 nm of nm in a short synthesis time period. The antibacterial and antifungal properties of ultrasonically synthesized silver nanomaterials (US-AgNPs) were also investigated. US-AgNPs are important nanomaterials that can find many good applications in practice.

Fast and Facile Microwave Synthesis of Cubic CuFe2O4 Nanoparticles for Electrochemical CO2 Reduction

Electrochemical CO2 reduction is a promising strategy for the sustainable synthesis of carbon-based chemicals or fuels such as CO, or CH4.[1] Copper-based materials are of special interest due to their broad substrate scope. While copper itself is the first known metal catalyst able to directly yield CH4, CO, methanol, or C2+ products such as ethanol can also be obtained, e.g. from oxide derived catalysts.[2][3] Another interesting copper oxide is the spinel CuFe2O4, due to its versatile electronic and magnetic properties. Those can be tuned via variations in the cation distribution between octahedral and tetrahedral sites.[4] Changes in the cation distribution, or degree of inversion, can additionally lead to a structural transformation between the cubic and tetragonal form, due to the strong Jahn-Teller effect of Cu2+. Both degree of inversion and structure are strongly dependant on the synthesis conditions.[4]In this contribution we introduce a fast microwave-assisted solvothermal synthesis of cubic CuFe2O4. Very short synthesis times of 1 min and low temperatures of 120 °C in ethylene-glycol/water mixtures could be realised, without a loss of phase-purity and no necessity for subsequent thermal treatment.[5] The degree of inversion was found to decrease with increasing synthesis time, whereas the particle size and crystallinity was almost independent of the synthesis conditions. The influence of the synthesis conditions – and thus material properties – on the activity in electrochemical CO2 reduction to CO in 0.1 M KHCO3 was investigated. The best activity was obtained for CuFe2O4 with an intermediate degree of inversion of approx. 0.75, together with a large crystallite size and micro-strain. Since hydrogen was produced as the only side-product, CuFe2O4 can be an interesting candidate for the production of syngas.

Challenges of Scaling-up the Wet-Chemical Synthesis of β-Li3PS4

All-solid-state batteries are considered the next generation in battery technology due to increased energy and power density as well as freedom of design, e.g. by constructing batteries in bipolar stacks. Solid-state electrolytes offer advantages over conventional liquid electrolytes, such as greater thermal safety, because of high melting points, and higher mechanical strength. This is believed to suppress growth of lithium dendrites and, therefore, opens up the possibility of using a lithium metal anode. One promising material group is sulfides, because they are ductile and have a good intrinsic ionic conductivity. Some sulfide solid electrolytes can be synthesized wet-chemically. This offers advantages like tailoring the particle size, working at ambient temperatures, short synthesis durations, stabilizing meta-stable phases by using new synthesis routes and the possibility of transferring the routine to a continuous process. The particle size and morphology are important factors regarding the suitability to produce all-solid-state batteries wherefore small (< 10 µm) and homogeneous particles are preferred. The present research mainly focusses on finding and improving new materials and their usage in battery production, but there is little progress on mass-production of sulfide solid electrolytes. To scale-up a synthesis, multiple aspects have to be considered since they often influence both product and process. Therefore, an analysis and optimization of the synthesis process is necessary to support the development and to increase the economic attractiveness of new materials.In this presentation, the reaction enthalpy and the influences of concentration and solvent variation of synthesizing the sulfide solid electrolyte β-Li3PS4 are examined and discussed. β-Li3PS4 is synthesized by mixing lithium sulfide and phosphorus pentasulfide in a solvent, e.g. THF, at ambient conditions. After removing the solvent, heat treatment is used to obtain the crystalline product. We found that the mixing step contains a highly exothermic reaction and determined the reaction enthalpies using a reaction calorimeter. To handle the heat development, two options were investigated: First, the solvent amount was increased and second, the synthesis was performed using alternative solvents with different thermal properties. The examined solvents are THF, ethyl acetate and ethyl propionate. The reaction enthalpies of the synthesis in different solvents are compared. A strong influence on the particle size and morphology caused by the amount and choice of solvent could be detected by SEM. While the particle size increases with increasing amount of solvent, the shape of the particles alters under solvent variation. With low solvent amount the smallest particle sizes (< 10 µm) are synthesized. Finally, suggestions regarding the scale-up will be given based on the findings of these examinations.

Synthesis, antibiofilm activity and molecular docking of N-acylhomoserine lactones containing cinammic moieties

We prepared a series of cinnamoyl-containing furanones by an affordable and short synthesis. The nineteen compounds hold a variety of substituents including electron-donating, electron-withdrawing, bulky and meta-substituted phenyls, as well as heterocyclic rings. Compounds showed antibiofilm activity in S. aureus, K. pneumoniae and, more pronounced, against P. aeruginosa. The disruption of quorum sensing (QS) was tested using the violacein test and molecular docking predicted the antagonism of LasR as a plausible mechanism of action. The trimethoxylated and diene derivatives showed the best antibiofilm and anti-QS properties, thus becoming candidates for further modifications.

Synthesis and Olfactory Properties of Lower‐Ring Homologues of the Linear Alicyclic Musk Romandolide

AbstractIn order to expand the knowledge on linear alicyclic musks, a set of 29 small‐ring (racemic) analogues of the biodegradable and renewable alicyclic musk Romandolide was designed, prepared, and evaluated. The common short and modular synthesis employs either commercially available or easily accessible (substituted) cyclopropyl/cyclobutyl ketones and acids. These were transformed in three/four steps to the target compounds. Their qualitative olfactory analysis reveals that contraction of cyclohexane ring of Romandolide to smaller rings annihilates the genuine musk scent, though many of these share the metallic hot‐iron off‐note of some macrocyclic musks. Indeed, these new derivatives exhibit a plethora of pleasant, interesting, and potentially useful scents including herbal, green, fruity, or chocolate ones accompanied by various undertones. The powdery, fruity ionone odor of the dimethyl cyclobutyl compound was found to be most interesting as it possesses a very natural raspberry and violet character. Computational modelling suggest that the lowest‐energy conformers of the target compounds do either not adopt a true U‐shape as was speculated to be a prerequisite for a musk odor, or that the quaternary carbon atom of the dimethyl‐substituted cyclobutane is not well placed to fit into a hydrophobic binding pocket on the corresponding receptor site.

Synthesis and characterization of four diastereomers of β-lactamase inhibitor drug intermediate

A short and efficient stereo-specific synthesis of three stereoisomers (two diastereomer and one enantiomer) of Oxalate salt of benzyl (2S,5R)-5-(benzyloxyamino)piperidine-2-carboxylate (8) has been described. Compound 8 is a key intermediate in the synthesis of β-lactamase inhibitors, was synthesized in high diastereomeric excess using chirally pure L-pyroglutamic acid. In this report, we also describe a chiral high performance liquid chromatography (CHPLC) method to separate these isomers. The developed CHPLC method was validated for the accurate determination of the diastereomeric purity of compound 8.

Synthesis of Ca-Mg-Al layered double hydroxide from dolomite with ultrasound-assisted method. Application in phosphate removal

The aim of this work was to obtain a Layered Double Hydroxide (LDH) from natural dolomite and to apply the synthetized solid (CaMgAl-LDH) for phosphate removal by adsorption. Both the conventional coprecipitation method and ultrasound-assisted method were used to obtain CaMgAl-LDH. The obtained solids were characterized by N2 adsorption/desorption, size of pores, X-ray diffraction, and FTIR. Batch scale experiments were carried out to evaluate the phosphate adsorption capacity on CaMgAl-LDH using design of experiments (DOE). The studied parameters were pH, solid dosage, contact time and phosphate removal percentage, which was selected as the response function. Experimental data were fitted to kinetics and isotherms mathematical models. The process thermodynamics was also studied. Results showed that the ultrasound-assisted method was more efficient to obtain LDH even in a short period of sonication. The solids presented good crystallization, structure between layers, and high purity. Besides, LDH obtained by ultrasound exhibited a surface area of ​​about 40% greater than the LDH obtained by the conventional method. The results of LDH application for phosphate removal showed high adsorption capacity (>94%) in several conditions of contact time and pH, even in low solid dosage. The kinetics of the process followed the pseudo-second-order model and Redlich-Peterson was the isotherm model that presented the best adjust. The thermodynamic parameters suggested a spontaneous, endothermic, and randomness process at the solid/solution interface, confirming an adsorption system favorable. The results exhibited that the ultrasound-assisted method is promissory to obtain LDH from mineral sources such as dolomite due to decrease energy expenditure and short synthesis time. It was found the ultrasound-assisted method also improve the solid physicochemical characteristics for its use in the adsorption process, enhancing the phosphate removal.

ZIF-8 with exceptional thermal stability: Role of organic cosolvents in phase control and structure stabilization

Thermal stability is one of the key factors in catalysis and high-temperature industrial applications. The thermal degradation of ZIF-8, particularly its nanocrystals, could result in a significant loss of surface area and crystallinity, limiting its large-scale applicability. In this study, ZIF-8 nanocrystals with improved thermal stability were synthesized at room temperature (RT) through a facile, one-pot method – an ultrasound-assisted, solvent-guided ZIF-8 growth. The effect of synthesis variables, including the type and concentration of solvent, ultrasonication, and synthesis time, in improving the material’s thermal stability was studied systematically. The as-prepared samples were analyzed by TGA/DSC, XRD, SEM/TEM, FTIR, and BET to monitor the weight loss with temperature, sample crystallinity, crystal morphology, chemical structure, and surface area. Notably, synthesis with 5 v/v% of n-hexane (ZIF-8new-ref) demonstrated the formation of highly-crystalline ZIF-8 nanocrystals with extraordinary thermal stability (with only ∼2.0–3.0 % weight loss up to 600 °C), large surface area (i.e., 975 m2 g−1), and an excellent particle size distribution in the range of 0.2–0.4 μm. More importantly, the short synthesis time (2 h) and sonication-assisted pretreatment of the precursor (for promoting solvent-ligand interaction) proved effective and played a crucial role in controlling ZIF-8’s thermal stability. The mechanism for the thermal stability enhancement was thus proposed. The highly thermally stable ZIF-8 nanocrystals were also synthesized with significantly reduced chemical usage, e.g., 1/11 of the normal ligand-to-metal ratio (70), achieving cost-effective and environmentally friendly synthesis.

Panaceum. O leczniczych walorach wina od starożytności po współczesność

The article is a short synthesis of the long history of wine used as a universal medicine from antiquity to the present day. The author, as a cultural anthropologist, does not focus on the problems and pathologies that are usually encountered in contemporary medical publications on alcohol. He shows the reasons why the dominant narratives about wine and other alcoholic beverages changed at the end of the 19th century, and expresses hope for the reconstruction of the proper proportions.

A methodological approach by capillary electrophoresis coupled to mass spectrometry via electrospray interface for the characterization of short synthetic peptides towards the conception of self-assembled nanotheranostic agents

Nanostructures formed by the self-assembling peptide building blocks are attractive materials for the design of theranostic objects due to their intrinsic biocompatibility, accessible surface chemistry as well as cavitary morphology. Short peptide synthesis and modification are straightforward and give access to a great diversity of sequences, making them very versatile building blocks allowing for the design of thoroughly controlled self-assembled nanostructures. In this work, we developed a new CE-DAD-ESI-MS method to characterize short synthetic amphiphilic peptides in terms of exact sequence and purity level in the low 0.1 mg.mL−1 range, without sample treatment. This study was conducted using a model sequence, described to have pH sensitive self-assembling property. Peptide samples obtained from different synthesis processes (batch or flow, purified or not) were thus separated by capillary zone electrophoresis (CZE). The associated dual UV and MS detection mode allowed to evidence the exact sequence together with the presence of impurities, identified as truncated or non-deprotected sequences, and to quantify their relative proportion in the peptide mixture. Our results demonstrate that the developed CE-DAD-ESI-MS method could be directly applied to the characterization of crude synthetic peptide products, in parallel with the optimization of peptide synthetic pathway to obtain controlled sequences with high synthetic yield and purity, which is crucial for further design of robust peptide based self-assembled nanoarchitectures.

Synthesis of nominal phragmunis A, a natural product from the poisonous mushroom Trogia venenata

The mushroom-derived natural product phragmunis A is of medicinal interest due to its reported activity against the deadly brain cancer glioblastoma multiforme. Herein, we report a short synthesis of the nominal phragmunis A structure; the NMR spectroscopic data for the synthetic sample contains several significant differences to the those reported for the natural product. Efforts to structurally re-assign phragmunis A have been stymied by our failure to secure an authentic sample and the absence of any NMR spectra for the natural product. Thus, the correct structure remains a mystery at present.

A Simple Entry to the 5,8-Disubstituted Indolizidine Skeleton via Hetero Diels-Alder Reaction.

The 5,8-disubstituted indolizidines are the largest family of indolizidines isolated from the skin of amphibians. These compounds exhibit interesting biological activities such as noncompetitive blockers of nicotinic receptors. In this paper, we present a short, simple, and general synthesis of these alkaloids based on the hetero Diels-Alder reaction between suitable monoactivated dienes and Δ1-pyrroline as the dienophile. The selectivity of the process is explained based on computational studies. Concise synthesis of the indolizidine alkaloid 181B from a hetero Diels-Alder reaction was accomplished in four steps.

“Mind the Leadership Gap!”

The coronavirus pandemic has acted as a catalyst for organisational change, disrupting historic ways of working, and spearheading organisations towards the next evolution of their working environments. In the aftermath of the largest concurrent work from home experiment in the world, organisations are coming to grips with the new policies and practices they need to implement to remain competitive. But there is one crucial stakeholder who continues to be left out in academic research, leaders. New questions now arise as to how we should remodel leadership in an increasingly remote world. What skills do leaders need to develop and how, in order to maintain employee wellbeing and manage the intergenerational divide? This paper presents a short synthesis of the challenges faced by leaders today specifically around remote team management but also in the context of a multigenerational workforce, alongside a summary of the research gaps we face in post-COVID literature. This paper concludes with the production of a future research agenda for scholars to close this gap, and to help organisations in building their leadership capability in the ‘new normal’.