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Angewandte Chemie (Weinheim An Der... Jan 2024Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the...
Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the first example of allenoate activation by using chiral isochalcogenoureas (IChU) for formal (4+2) cycloaddition reactions. Compared to established phosphine and amine catalysis, the use of these easily available Lewis bases enables new stereoselective reaction pathways proceeding with high enantioselectivities, diastereoselectivities, and in good yields. In addition, the factors governing enantioselectivity and the origin of the observed differences compared to other commonly used Lewis bases are explained.
PubMed: 38549953
DOI: 10.1002/ange.202315345 -
ACS Applied Polymer Materials Mar 2024Imine-based vitrimers were prepared from synthesized diimine-dimethacrylate monomer derived from biobased vanillin. First, a methacrylate derivative starting from...
Imine-based vitrimers were prepared from synthesized diimine-dimethacrylate monomer derived from biobased vanillin. First, a methacrylate derivative starting from vanillin was synthesized. The diimine derivative was synthesized by condensation of the aldehyde groups from two vanillin methacrylate units with the amine groups of hexamethylenediamine (HMDA). The synthesized product was used in formulations containing ethylene glycol phenyl ether methacrylate (EGPMA) as a reactive diluent for the customization of final material properties and cured by exposure to ultraviolet (UV)-light using suitable radical photoinitiators or else with temperature using a radical thermal initiator. Materials with glass transition temperatures (s) ranging from 70 to 90 °C were prepared, showing good thermal stability and mechanical and thermomechanical properties. The evaluation of their vitrimeric characteristics revealed that all materials achieved a stress-relaxation factor (σ = 0.37σ) in less than 130 s at 160 °C, with photocured materials exhibiting faster relaxation rates. The catalytic effect of phosphine oxide groups in imine metathesis has also been evidenced. All prepared materials could be mechanically recycled and completely solubilized in a two-step degradation process, putting evidence of their potential use for carbon fiber-reinforced composites (CFRCs). In addition, they demonstrated promising self-repairing abilities. Finally, as a proof of concept, it was established that these formulations could be effectively processed using a Digital Light Processing three-dimensional (3D) Printer (DLP), resulting in the fabrication of complex shapes with high resolution.
PubMed: 38544971
DOI: 10.1021/acsapm.3c03234 -
Journal of the American Chemical Society Apr 2024Recognition-encoded melamine oligomers (REMO) are synthetic polymers that feature an alternating 1,3,5-triazine-piperazine backbone and side-chains equipped with either...
Recognition-encoded melamine oligomers (REMO) are synthetic polymers that feature an alternating 1,3,5-triazine-piperazine backbone and side-chains equipped with either a phenol or phosphine oxide recognition unit. An automated method for the solid-phase synthesis (SPS) of REMO of any specified sequence has been developed starting from dichlorotriazine monomer building blocks. Complementary homo-oligomers with either six phenols or six phosphine oxides were synthesized and shown to form a stable duplex in nonpolar solvents by NMR denaturation experiments. The duplex was covalently trapped by equipping the ends of the oligomers with an azide and an alkyne group and using a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The SPS methodology was adapted to synthesize mixed sequence libraries by using a mixture of two different dichlorotriazine building blocks in each coupling cycle of an oligomer synthesis. The resulting libraries contain statistical mixtures of all possible sequences. The self-assembly properties of these libraries were screened by using the CuAAC reaction to trap any duplexes present. In mixed sequence libraries of 6-mers, the trapping experiments showed that only sequence-complementary oligomers formed duplexes at micromolar concentrations in dichloromethane. The automated synthesis approach developed here provides access to large libraries of mixed sequence synthetic polymers, and the covalent trapping experiment provides a convenient tool for screening functional properties of mixtures. The results suggest high-fidelity sequence-selective duplex formation in mixtures of 6-mer sequences of the REMO architecture.
PubMed: 38529806
DOI: 10.1021/jacs.4c01381 -
Organic Letters Apr 2024In this Letter, we report a direct and robust desulfurization method employing water-soluble phosphine, specifically tris(2-carboxyethyl)phosphine hydrochloride (TCEP),...
In this Letter, we report a direct and robust desulfurization method employing water-soluble phosphine, specifically tris(2-carboxyethyl)phosphine hydrochloride (TCEP), and tetrahydroxydiboron (B(OH)), which serves as a radical initiator. This innovative reaction exhibits compatibility with a diverse array of substrates, including cysteine residues in chemically synthesized oligopeptides and cyclic peptides, alkyl thiols in bioactive molecules, disulfides in commercial proteins, and selenocysteine. We optimized the reaction conditions to minimize the formation of undesired oxidized and borylated byproducts. Furthermore, the refined desulfurization process is executed after native chemical ligation (NCL) in a single pot, streamlining the existing synthetic approaches. This demonstrates its potential applications in the synthesis of complex peptides and proteins, showcasing a significant advancement in the field.
Topics: Indicators and Reagents; Peptides; Proteins; Cysteine; Sulfhydryl Compounds
PubMed: 38517348
DOI: 10.1021/acs.orglett.4c00609 -
Applied Microbiology and Biotechnology Mar 2024Microalgae are rich in fatty acids, proteins, and other nutrients, which have gained the general attention of researchers all over the world. For the development of...
Microalgae are rich in fatty acids, proteins, and other nutrients, which have gained the general attention of researchers all over the world. For the development of Chlorella vulgaris in food and feed industry, this study was conducted to investigate the differences in C. vulgaris' growth and nutritional components under different culture conditions (autotrophic, heterotrophic, photoheterotrophic) and the internal factors through cell counting in combination with transcriptome and nutrient analyses. The results showed that, under the photoheterotrophic condition, Chlorella's growth and the contents of lipid and protein were significantly higher than that under the heterotrophic condition, and the moisture content was lower than that under the heterotrophic condition. The saturated fatty acid content under the photoheterotrophic condition was the lowest, while the polyunsaturated fatty acid content was significantly higher than those under the other two conditions. There were 46,583 differentially expressed genes (DEGs), including 33,039 up-regulated DEGs (70.93%) and 13,544 down-regulated DEGs (29.07%), under the photoheterotrophic condition in comparison with the autotrophic condition. The fold change between the two conditions of samples of up-regulated genes was higher than that of the down-regulated genes. The KEGG enrichment showed that the up-regulated DEGs in the photoheterotrophic condition were significantly enriched in 5 pathways, including protein processing in endoplasmic reticulum pathway, photosynthesis pathway, photosynthesis-antenna protein pathway, endocytosis pathway, and phosphonate and phosphinate metabolism pathway. DEGs related to fatty acid metabolic pathways were significantly enriched in the fatty acid biosynthesis pathway and the biosynthesis of unsaturated fatty acid pathway. The qPCR analysis showed that the expression pattern of the selected genes was consistent with that of transcriptome analysis. The results of this study lay a theoretical foundation for the large-scale production of Chlorella and its application in food, feed, and biodiesel. KEY POINTS: • Nutrient levels under photoheterotrophic condition were higher than other conditions. • Six important pathways were discovered that affect changes in nutritional composition. • Explored genes encode important enzymes in the differential metabolic pathways.
Topics: Chlorella vulgaris; Fatty Acids; Photosynthesis; Metabolic Networks and Pathways; Nutrients; Biomass; Microalgae; Biofuels
PubMed: 38507095
DOI: 10.1007/s00253-024-13090-w -
Bioorganic & Medicinal Chemistry Apr 2024Reactions for drug synthesis under cell-like conditions or even inside living cells can potentially be used e.g., to minimize toxic side effects, to maximize bioactive...
Reactions for drug synthesis under cell-like conditions or even inside living cells can potentially be used e.g., to minimize toxic side effects, to maximize bioactive compound efficacy and/or to address drug delivery problems. Those reactions should be bioorthogonal to enable the generation of drug-like compounds with sufficiently good yields. In the known bioorthogonal Michael reactions, using thiols and phosphines as nucleophiles (e.g., in CS and CP bond formation reactions) is very common. No bioorthogonal Michael addition with a carbon nucleophile is known yet. Therefore, the development of such a reaction might be interesting for future drug discovery research. In this work, the metal-free Michael addition between cyclohexanone and various trans-β-nitrostyrenes (CC bond formation reaction), catalysed by a dipeptide salt H-Pro-Phe-ONa, was investigated for the first time in the presence of glutathione (GSH) and in phosphate-buffered saline (PBS). We demonstrated that with electron-withdrawing substituents on the aromatic ring and in β-position of the trans-β-nitrostyrene yields up to 64% can be obtained under physiological conditions, indicating a potential bioorthogonality of the studied Michael reaction. In addition, the selected Michael products demonstrated activity against human ovarian cancer cells A2780. This study opens up a new vista for forming bioactive compounds via CC bond formation Michael reactions under physiological (cell-like) conditions.
Topics: Humans; Female; Cell Line, Tumor; Ovarian Neoplasms; Carbon; Sulfhydryl Compounds
PubMed: 38492540
DOI: 10.1016/j.bmc.2024.117650 -
Advanced Science (Weinheim,... Jun 2024A series of new pyrazole-alkyl phosphine ligands with varying cycloalkyl ring sizes that enable additive-free regio- and chemoselective C─H arylation of heterocycles...
Regio- and Chemoselective Palladium-Catalyzed Additive-Free Direct C─H Functionalization of Heterocycles with Chloroaryl Triflates Using Pyrazole-Alkyl Phosphine Ligands.
A series of new pyrazole-alkyl phosphine ligands with varying cycloalkyl ring sizes that enable additive-free regio- and chemoselective C─H arylation of heterocycles are reported. Excellent α/β selectivity of various heterocycles such as benzo[b]thiophene, thiophene, furan, benzofuran, and thiazole can be achieved using these ligands, along with excellent chemoselectivity of C─Cl over C─OTf of chloroaryl triflates. Mechanistic studies supported by both experimental findings and density functional theory calculations indicate that the pyrazole phosphine ligands with optimal ring sizes allow the reaction to proceed with a lower energy barrier via a concerted metalation-deprotonation pathway.
PubMed: 38482750
DOI: 10.1002/advs.202309192 -
Journal of the American Chemical Society Mar 2024Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides...
Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation. A data-science-driven approach to substrate scope evaluation was coupled to high throughput experimentation (HTE) to facilitate statistical modeling in order to inform mechanistic studies. Reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis elucidated the turnover-limiting step to be the collapse of the tetrahedral intermediate and provided key insights into the catalyst-substrate structure-activity relationships responsible for the origin of the enantioselectivity. This study offers a reliable method for accessing enantioenriched sulfonimidamides to propel their application as pharmacophores and serves as an example of the mechanistic insight that can be gleaned from integrating data science and traditional physical organic techniques.
Topics: Molecular Structure; Stereoisomerism; Data Science; Cinchona Alkaloids; Catalysis; Acylation
PubMed: 38480482
DOI: 10.1021/jacs.4c00374 -
Advanced Science (Weinheim,... May 2024Despite the simplicity and abundance of ethylene, its practical application presents significant hurdles due to its nature as a highly flammable gas. Herein, a strategic...
Despite the simplicity and abundance of ethylene, its practical application presents significant hurdles due to its nature as a highly flammable gas. Herein, a strategic use of easily handled vinyl ether is reported as a latent ethylene surrogate achieved via a spin-center shift (SCS) pathway, enabling the successful three-component reaction that bridges heteroarenes and various coupling partners, including sulfinates, thiols, and phosphine oxides. Through a photoredox catalytic process, α-oxy radicals are generated by combining various radicals with phenyl vinyl ether, which are subsequently added to N-heteroarenes. Subsequently, the radical-mediated SCS pathway serves as the driving force for C─O bond cleavage, effectively engaging the phenoxy group as a leaving group. In addition, by broadening the utility of the method, a valuable synthon is provided for efficient C─H vinylation of N-heteroarenes following sulfonyl group elimination. This approach not only enriches the toolbox of synthetic methodology but also provides a more streamlined alternative, circumventing the challenges associated with direct ethylene gas usage. The versatility of the method, particularly evident in late-stage functionalizations of medicinally relevant molecules and peptides, underscores its capability to produce invaluable three-component compounds and vinylated N-heteroarene derivatives.
PubMed: 38477022
DOI: 10.1002/advs.202309800 -
Frontiers in Chemistry 2024Anhydrous hydrogen fluoride (AHF), a critical raw material for industries such as aluminum, pharmaceuticals, and petroleum, has traditionally been sourced from... (Review)
Review
Anhydrous hydrogen fluoride (AHF), a critical raw material for industries such as aluminum, pharmaceuticals, and petroleum, has traditionally been sourced from fluorite-a non-renewable mineral. The unsustainable reliance on fluorite has catalyzed the search for alternative AHF production methods. A promising substitute is fluorosilicic acid (FSA), a byproduct of the phosphate fertilizer industry previously deemed waste. Transforming fluorosilicic acid into AHF not only yields a valuable resource but also addresses the environmental and economic challenges associated with waste management. The innovative practice of producing AHF from fluorosilicic acid signals a shift towards sustainable chemical production by capitalizing on waste, potentially diminishing reliance on fluorite and reducing the industry's environmental impact. This review thoroughly dissects the AHF synthesis process from fluorosilicic acid. Despite the acknowledged importance of fluorinated compounds in numerous industrial applications, research on their synthesis from fluorosilicic acid is limited and fragmented. This review seeks to amalgamate this scattered information by closely scrutinizing diverse industrial processing methods. Additionally, it explores the current and future landscape, economic feasibility, and strategies to navigate the obstacles inherent in synthesizing AHF from fluorosilicic acid. It also assesses the environmental impact of these methods, thereby contributing to the dialogue in this emerging field. The primary aim of this manuscript is to foster further research and promote the industrial uptake of this sustainable process. Highlighting the challenges and proposing potential improvements, the review supports the responsible reuse of waste and advocates for advancements in industrial practices.
PubMed: 38476650
DOI: 10.3389/fchem.2024.1372981