Efficient Synthesis Research Articles

Regioselective Synthesis of Cycloalkane-fused Pyrazolo[4,3-e]pyridines through Tandem Reaction of 5-aminopyrazoles, Cyclic Ketones and Electron-rich Olefins.

Pyrazolopyridines are interesting fused heterocyclic pharmacophores that combine pyrazole and pyridine; two privileged nuclei extensively studied and with a wide range of applications. They can be obtained by a broad variety of synthetic methods among which multicomponent reactions have gained importance, especially from 5-aminopyrazoles and dielectrophilic reagents. However, the search for new approaches more in tune with sustainable chemistry and the use of unconventional heating in three-component synthesis are open and highly relevant study fields. A novel, practical and efficient three-component synthesis of cycloalkane-fused pyrazolo[ 4,3-e]pyridines was developed through a tandem reaction of 5-aminopyrazoles, cyclic ketones and electron-rich olefins, using microwave induction in perfluorinated solvent and iodine as catalyst. The microwave-induced three-component approach applied in this work promoted the construction of 10 new pyrazolopyridines with high speed and excellent control of regioselectivity, favoring the linear product with good yields; where the versatility of electron-rich olefins in iodine-catalyzed cascade heterocyclizations, granted the additional benefit of easy isolation and the possibility to reuse the fluorous phase. Although pyrazolopyridines have been synthetically explored because of their structural and biological properties, most of the reported synthetic methods use common or even toxic organic solvents and conventional heating or multi-step processes. In contrast, this study applied a multicomponent methodology in a single step by microwave induction and with the versatility provided in this case by the use of perfluorinated solvent, which allowed easy isolation of the final product and recovery of the fluorous phase.

Panel-based assessment of ecosystem condition as a platform for adaptive and knowledge driven management.

Ecosystems are subjected to increasing exposure to multiple anthropogenic drivers. This has led to the development of national and international accounting systems describing the condition of ecosystems, often based on few, highly aggregated indicators. Such accounting systems would benefit from a stronger theoretical and empirical underpinning of ecosystem dynamics. Operational tools for ecosystem management require understanding of natural ecosystem dynamics, consideration of uncertainty at all levels, means for quantifying driver-response relationships behind observed and anticipated future trajectories of change, and an efficient and transparent synthesis to inform knowledge-driven decision processes. There is hence a gap between highly aggregated indicator-based accounting tools and the need for explicit understanding and assessment of the links between multiple drivers and ecosystem condition as a foundation for informed and adaptive ecosystem management. We describe here an approach termed PAEC (Panel-based Assessment of Ecosystem Condition) for combining quantitative and qualitative elements of evidence and uncertainties into an integrated assessment of ecosystem condition at spatial scales relevant to management and monitoring. The PAEC protocol is founded on explicit predictions, termed phenomena, of how components of ecosystem structure and functions are changing as a result of acting drivers. The protocol tests these predictions with observations and combines these tests to assess the change in the condition of the ecosystem as a whole. PAEC includes explicit, quantitative or qualitative, assessments of uncertainty at different levels and integrates these in the final assessment. As proofs-of-concept we summarize the application of the PAEC protocol to a marine and a terrestrial ecosystem in Norway.

EMIM] [OAc]: An Efficient Ionic Liquid Medium for the Synthesis of New 4-(furan/pyrrole/thiophene-2-yl)-3, 4-dihydro-1H-chromeno [4,3-d] pyrimidine-2,5-diones and Molecular Docking Studies

Abstract: An efficient synthesis of Chromeno[b]pyrimidine derivatives 4 has been achieved by treating 4-hydroxy-2H-chromen-2-one 1, furan-2-carbaldehyde / 1H-pyrrole-2-carbaldehyde/ thiophene-2- carbaldehyde 2, and urea/thiourea 3 at 65-70 °C for 90-120 min using 1-Ethyl-3-methylimidazolium acetate as ionic liquid and medium with good yields 86-90%. This synthetic method has numerous advantages, including high yields, a simple protocol, environmental friendliness, brief reaction times, and mild reaction conditions. Using a catalytically active ionic liquid as the medium eliminates the need for a catalyst and a solvent. In this study, the docking score of the synthesized compounds was found to be between -8 to -9 kcal/mol similar to the co-crystal. Additionally, the compounds maintained their amino acid interactions with Tyr 281 (coagulation protein; 6WV3) and Thr 179 (tubulin polymerization protein; 5LYJ.pdb).

Hyperproduction of 7-dehydrocholesterol by rewiring the post-squalene module in lipid droplets of Saccharomyces cerevisiae

Lipid droplets (LDs) are specialized organelles that store neutral lipids to reduce the negative effects of lipotoxicity on cells. However, many neutral lipids are precursors for the synthesis of sterols and complex terpenoids, and this sequestration often greatly limits the efficient biosynthesis of sterols and complex terpenoids. In this study, taking 7-dehydrocholesterol (7-DHC) synthesis in Saccharomyces cerevisiae as an example, we revealed the blocking mechanism of LD sequestration on the efficient synthesis of metabolic products and found that LDs can sequester a significant amount of squalene, the precursor of 7-DHC, effectively preventing it from being directed toward the post-squalene pathway. Based on this, a post-squalene pathway was reconstructed on LDs, which resulted in a 28.7% increase in the 7-DHC titer, reaching 684.1 mg/L, whereas the squalene titer was reduced by approximately 97%. Subsequently, the triacylglycerol degradation pathway was weakened to release the storage space in LDs, and the esterification pathway was concurrently strengthened to guide 7-DHC storage within LDs, which further increased 7-DHC production, reaching 792.9 mg/L. Finally, by reducing the NADH/NAD+ ratio to alleviate the redox imbalance, the 7-DHC titer reached 867.6 mg/L in shake flask and 5.1 g/L in a 3-L bioreactor, which is the highest reported titer to date. In summary, this study provides new insights into the important role of LDs in sterol synthesis and offers a novel strategy for constructing cell factories for the efficient synthesis of sterol compounds.

Facile and Efficient Synthesis of Fluorosilicone Polymers by Using an Optimized Gradient Ring-Opening Reaction.

Fluorosilicone rubber is essential for sealing in extreme temperatures and non-polar environments due to its exceptional adaptability. However, achieving a high yield of fluorosilicone polymers with medium and high fluorine content remains a challenge. Herein, a facile gradient strategy is developed that involves modifying the method of cyclic monomer addition based on the rate of ring-opening polymerization (ROP), to improve yield and adjust fluorine content precisely. The polymerization process is designed and tailored based on the reaction rates of anionic ring-opening polymerization (AROP) and cationic ring-opening polymerization (CROP) via an efficient gradient strategy. The effects of the polymerization process on the viscosity and yield of vinyl fluorosilicone polymers and hydrofluorosilicone polymers are investigated and optimized. Notably, the as-prepared vinyl-terminated fluoromethylsilane with 60% fluorine content (FMS-Vi-60F) has a high yield (86.6%) and high viscosity (150000 mPa·s) in a short reaction time, which is superior to previous methods. Clearly, the gradient ring-opening method developed in this work provides a facile and efficient synthesis for fabricating fluorosilicone polymers with a high yield and tunable fluorine content.

Efficient Synthesis of 2‐Arylpropionitriles Via Selective Monomethylation of Aryl Acetonitriles Using an Easy to Handle Methylation Agent

AbstractA convenient and safe methylation protocol employing quaternary ammonium salts (PhMe3NI) as alternative methylating agents for the selective α‐methylation of arylacetonitriles is presented. This approach allows for the selective α‐methylation of arylacetonitriles, overcoming the limitations of existing techniques, while offering a practical and sustainable solution for late‐stage functionalization in medicinal chemistry. The straightforward and safe nature of this methodology makes it particularly well‐suited for applications in drug discovery. In our report, we present a diverse set of 18 examples, achieving yields of up to 76 %.

Efficient Synthesis and Biological Evaluation of Some New Pyrazolo[1,5‐a]pyrimidine Derivatives as Antimicrobial Activity

AbstractA series of new pyrazolo[1,5‐a]pyrimidine 4–15 derivatives were synthesized starting from 3,5‐diaminopyrazole derivatives 3 a,b as precursor using a simple, efficient procedure, and screened for their in‐vitro antimicrobial activities. All the synthesized compounds were fully characterized by IR, 1HNMR, 13CNMR, MS spectral data, and elemental analysis. Among the investigated against the antimicrobial activity, compounds 4 b, 4 d, 4 e, 8 b, 9 and 12 showed the best activity. The remaining compounds were found to have weak activity against gram‐positive and gram‐negative.

Catalytic Enantioselective Synthesis of Boron-Stereogenic and Axially Chiral BODIPYs via Rhodium(II)-Catalyzed C-H (Hetero)Arylation with Diazonaphthoquinones and Diazoindenines.

The molecular engineering of boron dipyrromethenes (BODIPYs) has garnered widespread attention due to their structural diversity enabling tailored physicochemical properties for optimal applications. However, catalytic enantioselective synthesis of structurally diverse boron-stereogenic BODIPYs through intermolecular desymmetrization and BODIPYs with atroposelectivity remains elusive. Here, we showcase rhodium(II)-catalyzed site-specific C-H (hetero)arylations of prochiral BODIPYs and polysubstituted BODIPYs with diazonaphthoquinonesand diazoindenines, providing efficient pathways for the rapid assembly of versatile (hetero)arylated boron-stereogenic and axially chiral BODIPYs through long-range desymmetrization and axial rotational restriction modes. The synthetic application of the procedures has been emphasized by the efficient synthesis of BODIPY derivatives with various functions. Photophysical properties, bioimaging, and lipid droplet-specific targeting capability of tailored BODIPYs are also demonstrated, indicating their promising applications in biomedical research, medicinal chemistry, and material science.

Efficient Synthesis of Bis(indolyl)methane Derivatives on Heterogeneous Ga‐MCM‐41‐SO3H Catalyst under Mild Conditions

AbstractWe are reporting a convenient method for the synthesis of bis(indolyl)methane derivatives from relatively cheap and commercially available chemicals such as indoles and aldehydes in a one‐pot procedure using Ga‐MCM‐41‐SO3H heterogeneous catalyst. Notably, the use of this catalyst has resulted in high yield of products (up to 98 %) under mild conditions, and the catalyst was found to be stable and reusable, retaining its highly catalytic activity even after five runs. Interestingly, two alkaloids Arsindoline A and Turbomycine B were successfully synthesized in the employment of this catalyst. These findings suggest that Ga‐MCM‐41‐SO3H could be a promising alternative to traditional acid homogeneous catalysts in the synthesis of bis(indolyl)methane derivatives, offering several advantages including ease of separation and reuse, high stability, and low toxicity.

Ketone Skeletal Modification via a Metallaphotoredox-Catalyzed Deacylation and Acylation Strategy.

Herein, we describe a dual catalytic strategy that employs dihydroquinazolinones, derived from ketone analogs, as versatile intermediates for acylation via α C-C cleavage with 2-pyridyl esters, facilitating the efficient synthesis of a variety of ketones. The reaction accommodates a wide range of ketones and carboxylic acids, showing tolerance to various functional groups. The versatility of this synthetic technique is further highlighted through its application in the late-stage modification of pharmaceuticals and biologically active natural products.

Efficient and one-pot synthesis of 2,4,5-trisubstituted imidazoles in the presence of CuI immobilized on LDH coated with 1,3-benzenedisulfonylamide

Efficient and one-pot synthesis of 2,4,5-trisubstituted imidazoles in the presence of CuI immobilized on LDH coated with 1,3-benzenedisulfonylamide

An Organometallic Umpolung Approach for Iron‐Mediated Propargylic C–H Etherification

The synthesis of propargyl ethers is an efficient way to access a variety of pharmaceuticals and natural products. However, direct etherification of simple alkynes via propargylic C–H activation remains largely underreported, while propargylic substitution of prefunctionalized alkyne starting materials remains the dominant method for the synthesis of propargyl ethers. Herein, we report an organometallic umpolung approach for iron‐mediated C–H propargylic etherification. The stepwise iron‐mediated C–H activation followed by mild oxidative functionalization enables the first use of unadorned alkynes to preferentially couple with alcohols for the efficient synthesis of synthetically important propargylic ethers with excellent functional group compatibility, chemoselectivity and regioselectivity.

An Organometallic Umpolung Approach for Iron-Mediated Propargylic C-H Etherification.

The synthesis of propargyl ethers is an efficient way to access a variety of pharmaceuticals and natural products. However, direct etherification of simple alkynes via propargylic C-H activation remains largely underreported, while propargylic substitution of prefunctionalized alkyne starting materials remains the dominant method for the synthesis of propargyl ethers. Herein, we report an organometallic umpolung approach for iron-mediated C-H propargylic etherification. The stepwise iron-mediated C-H activation followed by mild oxidative functionalization enables the first use of unadorned alkynes to preferentially couple with alcohols for the efficient synthesis of synthetically important propargylic ethers with excellent functional group compatibility, chemoselectivity and regioselectivity.

Thiourea-Driven Mild Synthesis of Photochromic Zeolite without H2 for Transient Information Storage.

The synthesis of hackmanite has been a topic of research for nearly 100 years, but up to now, the reported synthesis methods inevitably use reducing H2 to introduce the F-center through high-temperature calcination to make it change color, which extremely hinders its energy efficient large-scale synthesis before commercial applications. Herein, we present a facile route to synthesize hackmanite by using organic sulfur source thiourea as a precursor in a mild and hydrogen-free process. The synthesized hackmanite exhibits UVC-specific response, fast response, high contrast coloring, and fast fading at room temperature. In view of its photochromic features, a proof-of-concept is presented for transient information storage and burning-after-reading protection; the written information can be automatically erased within 8 min at room temperature.

An efficient and environmental friendly synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione in aqueous hydrotropic medium

An efficient and environmental friendly synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione in aqueous hydrotropic medium

Variability of plant transcriptomic responses under stress acclimation: a review from high throughput studies

Plant transcriptomes are complex entities shaped spatially and temporally by a multitude of stressors. The aim of this review was to summarize the most relevant transcriptomic responses to selected abiotic (UV radiation, chemical compounds, drought, suboptimal temperature) and biotic (bacteria, fungi, viruses, viroids) stress conditions in a variety of plant species, including model species, crops, and medicinal plants. Selected basic and applicative studies employing RNA-seq from various sequencing platforms and single-cell RNA-seq were involved. The transcriptomic responsiveness of various plant species and the diversity of affected gene families were discussed. Under stress acclimation, plant transcriptomes respond particularly dynamically. Stress response involved both distinct, but also similar gene families, depending on the species, tissue, and the quality and dosage of the stressor. We also noted the over-representation of transcriptomic data for some plant organs. Studies on plant transcriptomes allow for a better understanding of response strategies to environmental conditions. Functional analyses reveal the multitude of stress-affected genes as well as acclimatory mechanisms and suggest metabolome diversity, particularly among medicinal species. Extensive characterization of transcriptomic responses to stress would result in the development of new cultivars that would cope with stress more efficiently. These actions would include modern methodological tools, including advanced genetic engineering, as well as gene editing, especially for the expression of selected stress proteins in planta and for metabolic modifications that allow more efficient synthesis of secondary metabolites.

Efficient electrocatalytic urea synthesis from CO2 and nitrate over the scale-up produced FeNi alloy-decorated nanoporous carbon

Electrocatalytic urea synthesis provides a favorable strategy for conventional energy-consuming urea synthesis, but achieving large-scale catalyst synthesis with high catalytic efficiency remains challenging. Herein, we developed a simple method for the preparation of a series of FeNi-alloy-based catalysts, named FeNi@nC-T (n represents the content of nanoporous carbon as 1, 3, 5, 7 or 9 g and T = 900, 950, 1000 or 1100 °C), for highly performed urea synthesis via NO3− and CO2 co-reduction. The FeNi@7C-1000 achieved a high urea yield of 1041.33 mmol h−1 gFeNi−1 with a Faradaic efficiency of 15.56% at –1.2 V vs. RHE. Moreover, the scale-up synthesized FeNi@7C-950-S (over 140 g per batch) was achieved with its high catalytic performance and high stability maintained. Mechanism investigation illuminated that the Ni and Fe sites catalyze and stabilize the key *CO and *N intermediates and minimize the C–N coupling reaction barriers for highly efficient urea synthesis.

Dynamic Reconstruction of Cu Catalyst under Electrochemical NO Reduction to NH3.

The electrochemical reduction of nitric oxide (NO) to ammonia (NH3) offers a sustainable way of simultaneously treating the air pollutant and producing a useful chemical. Among catalyst candidates, Cu emerges as a stand-out choice for its superb NH3 selectivity and production rate. However, a comprehensive study concerning its catalytic behaviorin the NO reduction environment is lacking. Here, we unravel the dynamic rearrangement of Cu catalysts during NO reduction: the emergence of a bundled nanowire structure dependent on the applied potential. This unique structure is closely linked to an enhancement in double-layer capacitance, leading to a progressive increase in current density from 236 mA cm-2 by 20% over 1 h, while maintaining a Faradaic efficiency of 95% for NH3. Characterizations of Cu oxidation states suggest that the nanostructure results from the dissolution-redeposition of Cu in the aqueous electrolyte, influenced by the interaction with NO or other reactive intermediates. This understanding contributes to the broader exploration of Cu-based catalysts for sustainable and efficient NH3 synthesis from NO.

Dynamic Lock-And-Release Mechanism Enables Reduced ΔG at Low Temperatures for High-Performance Polyanionic Cathode in Sodium-Ion Batteries.

Low-temperature synthesis of polyanionic cathodes for sodium-ion batteries is highly desirable but often plagued by prolonged reaction times and suboptimal crystallinity. To address these challenges, a novel self-adaptive coordination field regulation (SACFR) strategy based on a dynamic lock-and-release (DLR) mechanism is introduced. Specifically, urea is used as a DLR carrier during synthesis, which dynamically "locks" and "releases" vanadium ions for controlled release, simultaneously "locking" H+ ions to enhance phosphate group release, thereby creating a self-adaptive coordination field that can intelligently respond to real-time demands of the reaction system. This dynamic coordination behavior contributes to both an improvement in reaction kinetics and a significant reduction in Gibbs free energy change (ΔG). As a result, the kinetic efficiency and thermodynamic spontaneity of the reaction are greatly enhanced, enabling the efficient synthesis of high-crystalline Na3V2O2(PO4)2F (NVOPF) at 90 °C within just 3 hours. The as-prepared NVOPF cathode exhibits exceptional rate performance and ultra-stable cycling stability across a broad temperature range. Furthermore, the successful kilogram-scale synthesis underscores the practical potential of the innovative strategy. This work pioneers the regulation of coordination field chemistry for polyanionic cathode synthesis, providing transformative insights into material design.

Engineering Escherichia coli via introduction of the isopentenol utilization pathway to effectively produce geranyllinalool

BackgroundGeranyllinalool, a natural diterpenoid found in plants, has a floral and woody aroma, making it valuable in flavors and fragrances. Currently, its synthesis primarily depends on chemical methods, which are environmentally harmful and economically unsustainable. Microbial synthesis through metabolic engineering has shown potential for producing geranyllinalool. However, achieving efficient synthesis remains challenging owing to the limited availability of terpenoid precursors in microorganisms. Thus, an artificial isopentenol utilization pathway (IUP) was constructed and introduced in Escherichia coli to enhance precursor availability and further improve terpenoid synthesis.ResultsWe first constructed an artificial IUP in E. coli to enhance the supply of precursor geranylgeranyl diphosphate (GGPP) and then screened geranyllinalool synthases from plants to achieve efficient synthesis of geranyllinalool (274.78 ± 2.48 mg/L). To further improve geranyllinalool synthesis, we optimized various cultivation factors, including carbon source, IPTG concentration, and prenol addition and obtained 447.51 ± 6.92 mg/L of geranyllinalool after 72 h of shaken flask fermentation. Moreover, a scaled-up production in a 5-L fermenter was investigated to give 2.06 g/L of geranyllinalool through fed-batch fermentation. To the best of our knowledge, this is the highest reported titer so far.ConclusionsEfficient synthesis of geranyllinalool in E. coli can be achieved through a two-step pathway and optimization of culture conditions. The findings of this study provide valuable insights into the production of other terpenoids in E. coli.