Monthly Archives: September 2023

DBU Promoted Deformylative/Dehalogenative Difunctionalization to Access β‐Bromovinyl Aldehydes Derived from Tetralones

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DBU Promoted Deformylative/Dehalogenative Difunctionalization to Access β-Bromovinyl Aldehydes Derived from Tetralones**

Metal-free deformylative/dehalogenative carbonylation, Michael addition of β-bromovinyl aldehydes for the synthesis of δ-oxo esters and vinyl ethers have been reported. Nucleophilic and organo-catalytic behaviour of DBU is explored and the regeneration of the parent starting material from the vinyl ether is also highlighted.


Abstract

Herein we have disclosed metal-free 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU)-catalyzed protocol for the deformylative/dehalogenative carbonylation and Michael addition of β-bromovinyl aldehydes with acrylates and carbonylation followed by etherification with benzyl bromides to synthesize δ-oxo esters and vinyl ethers respectively in good yields under an open atmosphere with broad substrate scope. Regeneration of starting material from vinyl ethers, organo-catalytic and nucleophilic behavior of DBU is also discussed.

An Indolin‐3‐imine Photobase and pH Sensitive Fluorophore

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An Indolin-3-imine Photobase and pH Sensitive Fluorophore

Touching base: The photobasicity and pH sensitivity of a fluorescent indolin-3-imine derivative is described. The fluorophore can deprotonate and sense weakly acidic protic solvents – a process enhanced by excited state proton transfer. Cell imaging experiments revealed that indolin-3-imine is a potential scaffold for fluorescence cell microscopy.


Abstract

This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pK a=8.3 of its conjugate acid) results in a significant red-shift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.

Solvatochromic Properties of (Iso)quinolylpyrrole‐Boron Difluoride Complexes Bearing N,N‐Diphenylanilinyl Group and Its Regio‐Effect

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Asymmetric boron complexes composed of (iso)quinolyl-pyrrole ligands possessing triphenylamine unit on the (iso)quinoline or pyrrole moieties were systematically prepared. Their optical properties were investigated in various organic solvents, and they showed solvatochromic properties, which were influenced by the π-structure of the ligands and the position of the electron-donor group. The degrees of changes in the emission-color drastically changed for regioisomeric chromophores 1 and 2. In this study, the solvatochromic properties of the compounds were investigated and described using both experimental and computational results.

Development and Crosslinking Properties of Psoralen‐Conjugated Triplex‐Forming Oligonucleotides as Antigene Tools Targeting Genome DNA

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Development and Crosslinking Properties of Psoralen-Conjugated Triplex-Forming Oligonucleotides as Antigene Tools Targeting Genome DNA

We conducted a close investigation of psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs). The triangular relationships between structural differences, photo-crosslinking efficiencies, and biological activities were examined. This research suggested that the photo-crosslinking of Ps-TFO did not reach a plateau under cell irradiation conditions, highlighting the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.


Abstract

Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been utilized for genome editing and anti-gene experiments for over thirty years. However, the research on Ps-TFOs employing artificial nucleotides is still limited, and their photo-crosslinking properties have not been thoroughly investigated in relation to biological activities. In this study, we extensively examined the photo-crosslinking properties of Ps-TFOs to provide fundamental insights for future Ps-TFO design. We developed novel Ps-TFOs containing 2′-O,4′-C-methylene-bridged nucleic acids (Ps-LNA-mixmer) and investigated their photo-crosslinking properties using stable cell lines that express firefly luciferase constitutively to evaluate the anti-gene activities of Ps-LNA-mixmer. As a result, Ps-LNA-mixmer successfully demonstrated suppression activity, and we presented the first-ever correlation between photo-crosslinking properties and their activities. Our findings also indicate that the photo-crosslinking process is insufficient under cell irradiation conditions (365 nm, 2 mW/cm2, 60 min). Therefore, our results highlight the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.

Small Molecules Targeting Human UDP‐GlcNAc 2‐Epimerase

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Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay. We validated nine of the primary actives with an orthogonal real-time NMR assay and verified their IC50 values in the low micromolar to nanomolar range manually. Stability and solubility studies revealed three compounds for further evaluation. Thermal shift assays, analytical size exclusion and interferometric scattering microscopy demonstrated that the GNE inhibitors acted on the oligomeric state of the protein. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) revealed which sections of GNE were shifted upon the addition of the inhibitors. In summary, we have identified three small molecules as GNE inhibitors with high potency in vitro, which serve as promising candidates to modulate sialic acid biosynthesis in more complex systems

Chemical Composition and Evaluation of Antibacterial, Antibiofilm and Mutagenic Potentials of a Propolis Sample from the Atlantic Forest of Midwest Brazil

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Sixteen triterpenoids with various skeletal types, five phenylpropanoid derivatives, and two flavonoids were isolated from a propolis sample produced by Apis mellifera collected in the Atlantic Forest of Midwest Brazil. Among these compounds, six triterpenes, namely 3β,20R-dihydroxylanost-24-en-3-yl-palmitate, (23E)-25-methoxycycloartan-23-en-3-one, 24-methylenecycloartenone, epi-lupeol, epi-a-amyrin, and epi-β-amyrin are being reported for the first time in propolis, while cycloartenone, (E)-cinnamyl benzoate, and (E)-cinnamyl cinnamate are new findings in Brazilian propolis. The presence of cycloartane- and lanostane-type triterpenoids, the latter being a class of compounds of restricted distribution in propolis worldwide, has not been reported in propolis from Midwest Brazil until now. The ethyl acetate phase obtained from the ethanol extract was effective in preventing biofilm formation by Staphylococcus aureus, with an inhibition rate of about 96% at 0.5 mg.mL-1, and with quercetin isolated as one of its active constituents. In contrast, the hexane phase exhibited notable antibacterial activity against Pseudomonas aeruginosa, inhibiting bacterial growth by 92% at 0.5 mg.mL-1; however, none of the triterpenoids isolated from this phase proved active against this pathogen. The ethanol extract was neither toxic nor mutagenic at the concentrations tested, as determined by the in vivo SMART assay on Drosophila melanogaster, even under conditions of high metabolic activation.

Polymeric Electrolytes for Solid‐state Lithium Ion Batteries: Structure Design, Electrochemical Properties and Cell Performances

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The solid-state electrolytes are keys to achieve high energy, safety and stability for lithium ion batteries. In this review, core indicators of solid polymer electrolytes are discussed in detail including ionic conductivity, interface compatibility, mechanical integrity and cycling stability. Besides, we have also summarized how above properties can be improved by the design strategy of functional monomers, groups and assembly of batteries. Structures and properties of polymers are investigated here to provide a basis for all-solid-state electrolyte design strategies of multi-component polymers. Meanwhile, adjustment strategies of quasi-solid-state polymer electrolytes such as adding functional additives and carrying out structural design have also been investigated, aiming at solving problems caused by simply adding liquids or small molecular plasticizer. We hope that fresh and established researchers can achieve a general perspective of solid polymer electrolytes via this review, and spur more extensive interests for exploration of high-performance lithium ion batteries.

Finding the right balance between tertiary amine steric effect and solvent polarity for the regioselectivity and kinetics of epichlorohydrin acetolysis

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Finding the right balance between tertiary amine steric effect and solvent polarity for the regioselectivity and kinetics of epichlorohydrin acetolysis

The effect of steric hindrances in tertiary amine and solvent polarity on the regioselectivity and kinetics of the reaction of epichlorohydrin with acetic acid were investigated. Correlations between the reaction rate and the parameters of nucleophilicity and structure of amines as well as the polarity of the solvent were established. The regioselectivity of the reaction was studied by 1H NMR spectroscopy by the ratio of regioisomeric reaction products.


Abstract

The asymmetric oxirane ring-opening reaction leading to the formation of regioisomeric chlorohydrin esters was studied in the reaction series “acetic acid–epichlorohydrin–tetrahydrofuran (nitrobenzene)–trialkylamine” by kinetic methods and FT-IR spectroscopy. The effect of solvent polarity and the structure of tertiary amines on the regioselectivity and reaction rate were studied. Tertiary amines with comparable basicity but different nucleophilicity and spatial structure were chosen as catalysts. It was shown that in solvents of different polarity, the components of the initial reaction system are present both as hydrogen-bonded complexes and as individual substances. The reaction orders with respect to acid and amine in solvents of different polarity were established. Correlations between the reaction rate and the parameters of nucleophilicity and structure of amines as well as the polarity of the solvent were established. The regioselectivity of the reaction was studied by 1H NMR spectroscopy using the ratio of regioisomeric reaction products. It was shown that the regioselectivity and rate of catalytic acetolysis of epichlorohydrin are effectively controlled by the structure of tertiary amines and the polarity of the solvent. The scheme of reaction regio-flows was detailed.

Metal‐Catalyzed Synthesis of Benzofused Five‐Membered N/O/S Heterocycles, a Progressive Area in Synthetic Chemistry

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Benzo-fused five-membered N/O/S heterocyclic compounds, such as indole, benzofuran, and benzothiophene, possessing a single heteroatom, have important applications in medicinal chemistry, agrochemistry, and material chemistry. Metal-catalyzed reactions are well-established synthetic pathways for the formation of C-X bonds, enabling the direct synthesis of heterocycles. This approach offers advantages over traditional methods, such as fewer steps, increased atom economy, low catalyst loading, regioselectivity, and stereoselectivity. Due to their widespread uses in the pharmaceutical industry, the formation of C-N, C-O, and C-S bonds has gained significant attention. This article focusses on the metal-catalysed synthesis and corresponding mechanistic approaches for N/O/S heterocycles, particularly indole, benzofuran, and benzothiophene, reviewing the progress of the past five years and discussing unexplored future opportunities.