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1.
Zubao Gan Deyun Cui Hongyun Zhang Ying Feng Liying Huang Yingying Gui Lu Gao Zhenlei Song 《Molecules (Basel, Switzerland)》2022,27(15)
(Ph3C)[BPh(F)4]-catalyzed Hosomi-Sakurai allylation of allylsilanes with β,γ-unsaturated α-ketoesters has been developed to give γ,γ-disubstituted α-ketoesters in high yields with excellent chemoselectivity. Preliminary mechanistic studies suggest that trityl cation dominates the catalysis, while the silyl cation plays a minor role. 相似文献
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Lu Zhang Rongxiu Zhu Aili Feng Changyin Zhao Lei Chen Guidong Feng Lei Liu 《Chemical science》2020,11(17):4444
The first non-enzymatic redox deracemization method using molecular oxygen as the terminal oxidant has been described. The one-pot deracemization of β,γ-alkynyl α-amino esters consisted of a copper-catalyzed aerobic oxidation and chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation with excellent functional group compatibility. By using benzothiazoline as the reducing reagent, an exclusive chemoselectivity at the C N bond over the C C bond was achieved, allowing for efficient deracemization of a series of α-amino esters bearing diverse α-alkynyl substituent patterns. The origins of chemo- and enantio-selectivities were elucidated by experimental and computational mechanistic investigation. The generality of the strategy is further demonstrated by efficient deracemization of β,γ-alkenyl α-amino esters.A one-pot deracemization of β,γ-alkynyl α-amino esters consisting of an aerobic oxidation and chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation has been described. 相似文献
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Vasiliki Vakali Michail Papadourakis Nikitas Georgiou Nikoletta Zoupanou Dimitrios A. Diamantis Uro Javornik Paraskevi Papakyriakopoulou Janez Plavec Georgia Valsami Andreas G. Tzakos Demeter Tzeli Zoe Cournia Thomas Mauromoustakos 《Molecules (Basel, Switzerland)》2022,27(17)
Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M−1) and 2,6Me-β-CD (770 M−1). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies. 相似文献
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Danielle M. Williams David C. Thorn Christopher M. Dobson Sarah Meehan Sophie E. Jackson Joanna M. Woodcock John A. Carver 《Molecules (Basel, Switzerland)》2021,26(20)
14-3-3 proteins are abundant, intramolecular proteins that play a pivotal role in cellular signal transduction by interacting with phosphorylated ligands. In addition, they are molecular chaperones that prevent protein unfolding and aggregation under cellular stress conditions in a similar manner to the unrelated small heat-shock proteins. In vivo, amyloid β (Aβ) and α-synuclein (α-syn) form amyloid fibrils in Alzheimer’s and Parkinson’s diseases, respectively, a process that is intimately linked to the diseases’ progression. The 14-3-3ζ isoform potently inhibited in vitro fibril formation of the 40-amino acid form of Aβ (Aβ40) but had little effect on α-syn aggregation. Solution-phase NMR spectroscopy of 15N-labeled Aβ40 and A53T α-syn determined that unlabeled 14-3-3ζ interacted preferentially with hydrophobic regions of Aβ40 (L11-H21 and G29-V40) and α-syn (V3-K10 and V40-K60). In both proteins, these regions adopt β-strands within the core of the amyloid fibrils prepared in vitro as well as those isolated from the inclusions of diseased individuals. The interaction with 14-3-3ζ is transient and occurs at the early stages of the fibrillar aggregation pathway to maintain the native, monomeric, and unfolded structure of Aβ40 and α-syn. The N-terminal regions of α-syn interacting with 14-3-3ζ correspond with those that interact with other molecular chaperones as monitored by in-cell NMR spectroscopy. 相似文献
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Zhixue Liu Weilei Zhou Jingjing Li Haoyang Zhang Xianyin Dai Yaohua Liu Yu Liu 《Chemical science》2020,11(18):4791
A unique fluorescent supramolecular assembly was constructed using coumarin-modified β-cyclodextrin as a reversible ratiometric probe and an adamantane-modified cyclic arginine–glycine–aspartate peptide as a cancer-targeting agent via host–guest inclusion complexation. Importantly, the coumarin-modified β-cyclodextrin not only showed higher sensitivity than the parent coumarin derivatives owing to the presence of numerous hydroxyl groups on the cyclodextrin but also provided a hydrophobic cavity for encapsulation of a cancer-targeting agent. The assembly showed a reversible and fast response to biothiols with a micromolar dissociation constant, as well as outstanding cancer cell permeability, which can be used for high-efficiency real-time monitoring of biothiols in cancer cells. This supramolecular assembly strategy endows the fluorescent probe with superior performance for dynamic sensing of biothiols.A unique fluorescent supramolecular assembly was constructed from coumarin-modified β-cyclodextrin and an adamantane-modified cyclic arginine–glycine–aspartate peptide for high-efficiency real-time monitoring of biothiols in cancer cells. 相似文献
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三组分双官能化反应是一种高效、简便构建C―C键、C―X键的方式. 双键广泛存在于众多有机化合物中, 对双键的双官能化反应研究有巨大的应用潜力. 本工作以Ni(COD)2为催化剂, 以芳基溴化镁、芳基溴化物为芳基化试剂, 实现了3-芳基-2-丙烯醛亚胺中碳碳双键的双芳基化反应. 该反应建立了一个新的镍催化α,β-不饱和醛的α,β-双芳基化方法, 可以高度区域选择性地向底物分子中引入两个不同取代的芳环, 得到多种2,3,3-三芳基丙醛骨架的产物. 利用这一反应作为核心步骤实现了天然产物Quebecol的简便合成. 机理研究表明, 该反应可能经历了亲核加成、金属交换、还原消除的历程. 相似文献
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The bifurcated σ-hole···σ-hole stacking interactions between organosulfur molecules, which are key components of organic optical and electronic materials, were investigated by using a combined method of the Cambridge Structural Database search and quantum chemical calculation. Due to the geometric constraints, the binding energy of one bifurcated σ-hole···σ-hole stacking interaction is in general smaller than the sum of the binding energies of two free monofurcated σ-hole···σ-hole stacking interactions. The bifurcated σ-hole···σ-hole stacking interactions are still of the dispersion-dominated noncovalent interactions. However, in contrast to the linear monofurcated σ-hole···σ-hole stacking interaction, the contribution of the electrostatic energy to the total attractive interaction energy increases significantly and the dispersion component of the total attractive interaction energy decreases significantly for the bifurcated σ-hole···σ-hole stacking interaction. Another important finding of this study is that the low-cost spin-component scaled zeroth-order symmetry-adapted perturbation theory performs perfectly in the study of the bifurcated σ-hole···σ-hole stacking interactions. This work will provide valuable information for the design and synthesis of novel organic optical and electronic materials. 相似文献
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Anne-Sophie Schou Jdal Tomasz Pawel Czaja Frans W. J. van den Berg Birthe Mller Jespersen Kim Lambertsen Larsen 《Molecules (Basel, Switzerland)》2021,26(8)
Cyclodextrins (CDs) are cyclic oligosaccharides that have found widespread application in numerous fields. CDs have revealed a number of various health benefits, making them potentially useful food supplements and nutraceuticals. In this study, the impact of α-, β-, and γ-CD at different concentrations (up to 8% of the flour weight) on the wheat dough and bread properties were investigated. The impact on dough properties was assessed by alveograph analysis, and it was found that especially β-CD affected the viscoelastic properties. This behavior correlates well with a direct interaction of the CDs with the proteins of the gluten network. The impact on bread volume and bread staling was also assessed. The bread volume was in general not significantly affected by the addition of up to 4% CD, except for 4% α-CD, which slightly increased the bread volume. Larger concentrations of CDs lead to decreasing bread volumes. Bread staling was investigated by texture analysis and low field nuclear magnetic resonance spectroscopy (LF-NMR) measurements, and no effect of the addition of CDs on the staling was observed. Up to 4% CD can, therefore, be added to wheat bread with only minor effects on the dough and bread properties. 相似文献
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Ming Liu Gan Wang Runjia Xu Chuanbin Shen Heyu Ni Ren Lai 《Molecules (Basel, Switzerland)》2021,26(16)
Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s−1) and high (1800 s−1) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s−1). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition. 相似文献
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A protocol of highly regio- and enantioselective copper-catalyzed hydroacylation of the non-terminal C C bond in 1,1-disubstituted terminal allenes with anhydrides has been developed. Both aromatic and aliphatic carboxylic anhydrides are applicable to the efficient construction of all carbon quarternary centers connected with a versatile C C bond and a useful ketone functionality. The synthetic potentials of the enantioenriched products have also been demonstrated. Density functional theory (DFT) calculations were performed to explain the steric outcome of the products: the hydroacylation proceeds through a six-membered transition state and the ligand-substrate steric interactions account for the observed enantioselectivity although the chiral ligand is far away from the to-be-genetated chiral center.A protocol of highly regio- and enantioselective copper-catalyzed hydroacylation of the non-terminal C C bond in 1,1-disubstituted terminal allenes with anhydrides has been developed. 相似文献
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The effects of β-cyclodextrin (β-CD) on the spectral properties and electrochemical behaviour of barbitone sodium were studied using electrochemical and optical techniques. The apparent changes in the UV-visible absorption spectrum and fluorescence quenching of the barbiturate upon addition of β-CD afford clear evidence of the inclusion complex formation of β-CD in aqueous solutions. The redox acitivity of barbitone sodium in both the absence and presence of β-CD was assessed by an electrochemical method in 0.05 M potassium nitrate-nitric acid (pH 1.8) solution. While the complexation reaction remains is equilibrium, the apparent formation constant of the inclusion complex could be obtained by either spectral or electrochemical methods. Quantitative evaluation of the data gave 326 l mol−1 under equilibrium conditions at 20°C. Possible conclusions are discussed on the basis of environmental changes around the barbiturate molecules on inclusion. 相似文献
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以γ-环糊精(γ-CD)为主体, 采用饱和水溶液法对客体二甲戊灵进行包合. 采用紫外光谱以等摩尔连续变化法确定包合物的包合比为1∶1; 红外光谱证明二甲戊灵的部分苯环结构可能进入了γ-CD的空腔; 热分析结果证明包合作用提升了二甲戊灵的熔点; 粉末X射线衍射谱图中新衍射峰的出现说明形成了新物相; 扫描电镜则直观展现了包合物的外观. 以上结果均表明形成了γ-CD-二甲戊灵包合物, 其包合平衡常数K=1123.99 L/mol. 包合作用使二甲戊灵的熔点从54 ℃升至75 ℃, 溶解度提高了约11.5倍, 包合物热贮稳定性达标, 为进一步将其加工成其它水基化农药剂型提供了可能. 相似文献
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Francesco Bavo Marco Pallavicini Rebecca Appiani Cristiano Bolchi 《Molecules (Basel, Switzerland)》2021,26(12)
The selectivity of α4β2 nAChR agonists over the α3β4 nicotinic receptor subtype, predominant in ganglia, primarily conditions their therapeutic range and it is still a complex and challenging issue for medicinal chemists and pharmacologists. Here, we investigate the determinants for such subtype selectivity in a series of more than forty α4β2 ligands we have previously reported, docking them into the structures of the two human subtypes, recently determined by cryo-electron microscopy. They are all pyrrolidine based analogues of the well-known α4β2 agonist N-methylprolinol pyridyl ether A-84543 and differ in the flexibility and pattern substitution of their aromatic portion. Indeed, the direct or water mediated interaction with hydrophilic residues of the relatively narrower β2 minus side through the elements decorating the aromatic ring and the stabilization of the latter by facing to the not conserved β2-Phe119 result as key distinctive features for the α4β2 affinity. Consistently, these compounds show, despite the structural similarity, very different α4β2 vs. α3β4 selectivities, from modest to very high, which relate to rigidity/extensibility degree of the portion containing the aromatic ring and to substitutions at the latter. Furthermore, the structural rationalization of the rat vs. human differences of α4β2 vs. α3β4 selectivity ratios is here proposed. 相似文献
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In an attempt to find novel plant growth regulators, a series of unsaturated cyclic α‐hydroxyphosphonates were synthesized by the addition reactions of 4‐aryl‐5,5‐dimethyl‐1,3,2‐dioxaphosphinane 2‐oxides with 5‐aryl‐2E,4E‐pentadienaldehydes. The cis and trans isomers of the products were isolated. The structures of all products were confirmed by elemental analyses and by NMR and IR spectroscopy or MS. The results of preliminary bioassay indicate that the title compounds possess potential inhibitory activity on the elongation of wheat coleoptile. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:266–268, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10039 相似文献
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Heterocyclic moieties, especially five and six-membered rings containing nitrogen, oxygen or sulfur atoms, are broadly distributed in nature. Among them, synthetic and natural alike are pharmacologically active compounds and have always been at the forefront of attention due to their pharmacological properties. Heterocycles can be divided into different groups based on the presence of characteristic structural motifs. The presence of β-amino acid and heterocyclic core in one compound is very interesting; additionally, it very often plays a vital role in their biological activity. Usually, such compounds are not considered to be chemicals containing a β-amino acid motif; however, considering them as this class of compounds may open new routes of their preparation and application as new drug precursors or even drugs. The possibility of their application as nonproteinogenic amino acid residues in peptide or peptide derivatives synthesis to prepare a new class of compounds is also promising. This review highlights the actual state of knowledge about β-amino acid moiety-containing heterocycles presenting antiviral, anti-inflammatory, antibacterial compounds, anaplastic lymphoma kinase (ALK) inhibitors, as well as agonist and antagonists of the receptors. 相似文献
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Shinhui Lee Woog Jung Sanung Eom Hye Duck Yeom Heui-Dong Park Junho H. Lee 《Molecules (Basel, Switzerland)》2021,26(9)
Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor’s ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative. 相似文献