Recent advances of green pretreatment techniques for quality control of natural products

A few advancing technologies for natural product analysis have been widely proposed, which focus on decreasing energy consumption and developing an environmentally sustainable manner. These green sample pretreatment and analysis methods following the green Analytical Chemistry (GAC) criteria have the advantage of improving the strategy of chemical analyses, promoting sustainable development to analytical laboratories, and reducing the negative effects of analysis experiments on the environment. A few minimized extraction methodologies have been proposed for replacing the traditional methods in the quality evaluation of natural products, mainly including solid-phase microextraction (SPME) and liquid phase microextraction (LPME). These procedures not only have no need for large numbers of samples and toxic reagent, but also spend a small amount of extraction and analytical time. This overview aims to list out the main green strategies on the application of quality evaluation and control for natural products in the past 3 years.     

Recent advances in fluorinated vinylstannanes and their synthetic utility

Fluorinated vinylstannanes have attracted much interest in recent years because they provided a useful and convenient methodology for the introduction of monofluoro, difluoro, trifluoro or polyfluoro functionality into organic molecules with retention of configuration, particularly in the synthesis of fluorine-containing naturally occurring compounds. The new methodologies discussed in this review are, therefore, potentially useful in organic synthesis particularly in the medicinal and agricultural chemistry for the synthesis of fluorine-containing biologically active compounds.     

Recent advances on discovery of enzyme inhibitors from natural products using bioactivity screening

The essence of enzymes is to keep the homeostasis and balance of humans by catalyzing metabolic responses and modulating cells. Suppression of an enzyme slows the progress of some diseases, making it a therapeutic target. Therefore, it is important to develop enzyme inhibitors by proper bioactivity screening strategies for the future treatment of some major diseases. In this review, we summarized the recent (2015–2020) applications of several screening strategies (electrophoretically mediated microanalysis, enzyme immobilization, affinity chromatography, and affinity ultrafiltration) in finding enzyme inhibitors from certain species of bioactive natural compounds of plant origin (flavonoids, alkaloids, phenolic acids, saponins, anthraquinones, coumarins). At the same time, the advantages and disadvantages of each strategy were also discussed, and the future possible development direction in enzyme inhibitor screening has been prospected. To sum up, it is expected to help readers select suitable screening strategies for enzyme inhibitors and provide useful information for the study of the biological effects of specific kinds of natural products.     

Synthesis of 5-(3-indolyl)oxazole natural products. Structure revision of Almazole D

The synthesis and utility of β-oxotryptamine and β-oxytryptophan ester synthons provide a convenient entry to 5-(3-indolyl)oxazole natural products leading to a structure revision of almazole D.     

Total syntheses of the highly potent anti-cancer polyacetylenes, (S)-18-hydroxyminquartynoic acid, (S)-minquartynoic acid and (E)-15,16-dihydrominquartynoic acid

The total syntheses of three polyacetylenic natural products, (S)-18-hydroxyminquartynoic acid (1), (S)-minquartynoic acid (2) and (E)-15,16-dihydrominquartynoic acid (3), has been achieved. The Cadiot-Chodkiewicz cross-coupling reaction was used as the key step for the construction of tetrayne and triyne units.     

Synthesis and properties of novel fluorinated epoxy resins based on 1,1-bis(4-glycidylesterphenyl)-1-(3′-trifluoromethylphenyl)-2,2,2-trifluoroethane

A novel fluorinated epoxy resin, 1,1-bis(4-glycidylesterphenyl)-1-(3′-trifluoromethylphenyl)-2,2,2-trifluoroethane (BGTF), was synthesized through a four-step procedure, which was then cured with hexahydro-4-methylphthalic anhydride (HMPA) and 4,4′-diaminodiphenyl-methane (DDM). As comparison, a commercial available epoxy resin, bisphenol A diglycidyl ether (BADGE), cured with the same curing agents was also investigated. We found that the BGTF gave the exothermic starting temperature lower than BADGE no mater what kind of curing agents applied, implying the reactivity of the former is higher than the latter. The fully cured fluorinated BGTF epoxy resins have good thermal stability with glass transition temperature of 170-175 °C and thermal decomposition temperature at 5% weight loss of 370-382 °C in nitrogen. The fluorinated BGTF epoxy resins also showed the mechanical properties as good as the commercial BADGE epoxy resins. The cured BGTF epoxy resins exhibited improved dielectric properties as compared with the BADGE epoxy resins with the dielectric constants and the dissipation factors lower than 3.3 and dissipation 2.8 × 10⁻³, respectively, which is related to the low polarizability of the C-F bond and the large free volume of CF₃ groups in the polymer. The BGTF epoxy resins also gave low water absorption because of the existence of hydrophobic fluorine atom.     

Towards the total synthesis of tashironin related allo-cedrane natural products: further exploitation of the oxidative dearomatization-IMDA-RCM triad based strategy

Synthetic studies directed towards allo-cedrane based, tashironin sibling natural products, involving some deft functional group manipulations on a preformed tetracyclic scaffold, are delineated.     

Reactive desorption electrospray ionization mass spectrometry (DESI-MS) of natural products of a marine alga

Presented here is the optimization and development of a desorption electrospray ionization mass spectrometry (DESI-MS) method for detecting natural products on tissue surfaces. Bromophycolides are algal diterpene-benzoate macrolide natural products that have been shown to inhibit growth of the marine fungal pathogen Lindra thalassiae. As such, they have been implicated in antimicrobial chemical defense. However, the defense mechanisms are not yet completely understood. Precise detection of these compounds on algal tissue surfaces under ambient conditions without any disruptive sample processing could shed more light onto the processes involved in chemical defense of marine organisms. Conventional DESI-MS directly on algal tissue showed relatively low sensitivity for bromophycolide detection. Sensitivity was greatly improved by the addition of various anions including Cl⁻, Br⁻, and CF₃COO⁻ into the DESI spray solvent. Chloride adduction gave the highest sensitivity for all assayed anions. Density functional optimization of the bromophycolide anionic complexes produced during DESI supported this observation by showing that the chloride complex has the most favorable binding energy. Optimized DESI protocols allowed the direct and unambiguous detection of bromophycolides, including A, B, and E, from the surface of untreated algal tissue. Figure Desorption Electrospray Ionization, a novel technique for mass spectrometric analysis under open air conditions reveals the presence of naturally-occurring antibiotics on the surface of marine algae. Ab-initio calculations and experimental results indicate that sensitiviity could be greatly enhanced by means of dynamic complexation of these antibiotics with various small anions during the dynamic desorption process. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Scalable total synthesis of (-)-berkelic acid by using a protecting-group-free strategy

Supply chain: the polycyclic core of (-)-berkelic acid (1) was constructed in just one step from very simple starting materials. The total synthesis of 1 involves a seven-step linear sequence. Protection/deprotection steps were avoided and all but the last step were performed on a gram scale. This synthesis could solve the supply problem associated with the exhaustion of the natural source.     

基于Ce(IV)分光光度法的天然产物抗氧化活性的评价

基于在H2SO4,Na2SO4介质中稳定存在的Ce(IV)的还原,在320 nm时,采用紫外可见分光光度计测定Ce(IV)吸光度,建立还原率与样品浓度的剂量关系,以线性关系的斜率为主要评价指标,评价样品的抗氧化活性。结果表明:针对5种结构相近的黄酮化合物,抗氧化活性顺序为:槲皮素>山奈酚>木犀草素>芹菜素>黄芩素;针对中药植物湖北旋覆花,抱石莲和吉祥草的提取物,正丁醇、乙酸乙酯部位是抗氧化活性成分的主体部位,但在旋覆花和抱石莲中,正丁醇部位抗氧化活性更强,而在吉祥草中,乙酸乙酯部位明显强于正丁醇部位;此外,不同提取方法得到的提取物抗氧化活性不同,低温回流和超声提取均可提高效率,但超声提取的时间应该控制在30 min以内。本评价方法操作简单,结果稳定可靠,检测限低,适合于天然产物抗氧化活性植物及活性部位的快速筛选。     

Synthesis and properties of new pyridine-bridged poly(ether-imide)s based on 4-(4-trifluoromethylphenyl)-2,6-bis[4-(4-aminophenoxy)phenyl]pyridine

A novel pyridine-containing aromatic diamine monomer, 4-(4-trifluoromethylphenyl)-2,6-bis[4-(4-aminophenoxy)phenyl]pyridine (FAPP), was synthesized via the modified Chichibabin pyridine synthesis of 4-(4-nitrophenoxy)-acetophenone with 4-trifluoromethyl-benzaldehyde, followed by a catalytic reduction. A series of fluorinated pyridine-bridged aromatic poly(ether-imide)s were prepared from the resulting diamine monomer with various aromatic dianhydrides via a conventional two-step process. The resulting polyimides exhibited good solubility in aprotic amide solvents and m-cresol, such as N,N-dimethylacetamide, N-methyl-2-pyrrolidone, and m-cresol, etc., which possessed the inherent viscosities of 0.76-0.91 dL/g. Strong and flexible poly(ether-imide) films were obtained, which showed excellent thermal properties with the glass transition temperatures of 268-353 °C, the temperature at 5% weight loss of 547-595 °C, and the residue at 700 °C of 65-74% in nitrogen, good mechanical properties with the tensile strengths of 87.6-104.2 MPa and elongations at breakage of 8.9-12.6%, and good optical transparency with the cut-off wavelengths of 357-380 nm, as well as low dielectric constants in the range of 2.49-3.04 at 1 MHz and low water uptake 0.43-0.69%. Furthermore, the resulted polyimides derived from FAPP were compared with non-fluorinated analogous polyimides and fluorinated analogous polyimides with trifluoromethyl groups in different positions, and the effects of substituents were also investigated and discussed.     

Recent advances on boron doped diamond (BDD) electrode as cathode in organic and inorganic preparative electrotransformations

Although anodic oxidation reactions mediated by boron-doped diamond (BDD) electrodes have been broadly studied, research on cathodic conversion remains still scarce despite the favorable characteristics of this electrode for such application. A detailed survey of the recent literature about processes in which boron-doped diamond electrode has been employed in cathodic reactions is presented, including inorganic species (O₂, CO₂, nitrate, metaborate) and organic compounds (carbonyl, nitro groups and halogenated compounds).     

Heat-resistant and soluble fluorinated poly(amide imide)s based on non-coplanar ortho-linked diimide-dicarboxylic acid

A series of novel fluorinated heat-resistant poly(amide imide)s (PAIS) based on non-coplanar diimide-diacid monomer (DIDA) were synthesized and characterized. The poly(amide imide)s were obtained in high yields and possessed inherent viscosities in the range of 0.47-0.91 dL g⁻¹. All of the polymers were amorphous in nature, showed outstanding solubility and could be readily soluble in common organic solvents such as N,N-dimethylacetamide, N-methyl-2-pyrrolidinoned, dimethyl sulfoxide, N,N-dimethylformamide, pyridine and tetrahydrofuran. Glass transition temperatures were in the range of 221-263 °C, as determined by differential scanning calorimetry. Degradation temperatures for 10% weight loss occurred all above 520 °C and char yields was more than 50% at 700 °C in nitrogen atmosphere. Moreover, these PAIs possessed low refractive indexes (n = 1.58-1.59), birefringence (Δn = 0.008-0.013), and dielectric constants (? ≈ 2.5) due to the trifluoromethyl pendent groups and ortho-catenated aromatic rings that interrupt chain packing and increase free volume.     

Synthesis and characterization of soluble polyimides based on a new fluorinated diamine: 4-Phenyl-2,6-bis[3-(4′-amino-2′-trifluoromethyl-phenoxy) phenyl] pyridine

A new kind of pyridine-containing aromatic diamine monomer, 4-phenyl-2,6-bis[3-(4′-amino-2′-trifluoromethyl-phenoxy) phenyl] pyridine (m-PAFP), was successfully synthesized by a modified Chichibabin reaction of 3-(4′-nitro-2′-trifluoro-methyl-phenoxy)-acetophenone with benzaldehyde, followed by a catalytic reduction. A series of fluorinated pyridine-bridged aromatic poly(ether-imide)s were prepared from the resulting diamine monomer with various aromatic dianhydrides via a conventional two-step thermal or chemical imidization method. The inherent viscosities values of these polyimides were in the range of 0.56-1.02 dL/g, and they could be cast and thermally converted into transparent, flexible, and tough polyimide films. The polyimides displayed higher solubility in polar solvents such as NMP, DMSO and m-cresol. The polyimides had good thermal stability, with the glass transition temperatures (T_g) of 187-211 °C, the temperatures at 5% weight loss of 511-532 °C, and the residue at 800 °C in air was higher than 50%. These films also had dielectric constants of 2.64-2.74 at 10 MHz and low water uptake 0.53-0.66%. Wide-angle X-ray diffraction measurements revealed that these polyimides were predominantly amorphous. Moreover, the polymer films of these novel polyimides showed outstanding mechanical properties with the tensile strengths of 90.1-96.6 MPa, elongations at breakage of 8.9-10.7% and tensile modulus of 1.65-1.98 GPa.     

Histone deacetylase (HDAC) inhibitor curcumin upregulates mitochondrial uncoupling protein1 (UCP1) and mitochondrial function in brown adipocytes,in-silico study and screening natural drug library

Mitochondrial dysfunction has been associated with diverse pathological conditions globally. Specifically, in adipose tissues, mitochondrial dysfunction is the primary cause of obesity and obesity-related illnesses. An existing drugs such as atorvastatin and other lipid-lowering drugs demonstrated adverse effects and initiated other diseases. Thus, we need to explore new methods to prevent and treat obesity. In this study, we used the cell screening method to identify several natural compounds that increase adipocyte UCP1 gene expression. The identified drug Curcumin was evaluated in cell models and the In-silico model. We found curcumin is an active compound of turmeric belonging to Zingiberaceae (ginger family), which activates the Nrf2 mechanism. Curcumin potentially endorses the expression of UCP1 in the brown adipocyte in vitro cellular model. Curcumin plays an important role that modulating mitochondrial function and improving mitochondrial DNA quantification, ATP production, and cell viability. We have established an efficient in vitro cell experiment system to study the metabolic regulation of UCP1. The in-silico model revealed curcumin-UCP1 interaction. Curcumin, via enhancing mitochondrial activity, could be a helpful therapeutic molecule against metabolic disorders or obesity-related diseases. Curcumin will be the subject of more research in both human and murine models, which will provide novel therapeutic pathways for the treatment of metabolic illnesses by modulating the control of mitochondrial function.     

Simultaneous extraction and determination of pharmaceuticals and personal care products (PPCPs) in river water and sewage by solid-phase extraction and liquid chromatography-tandem mass spectrometry

This study features the simultaneous extraction and quantification of 18 pharmaceuticals and personal care products (PPCPs). This is a pioneering method for the quantification of acetaminophen, sulfamethoxazole, diclofenac, atenolol, metoprolol, diethyltoluamide and oxybenzone in atmospheric pressure chemical ionisation mode. The method was validated for high repeatability and reproducibility with relative standard deviations less than 10%. Instrument quantification limits for PPCPs were within the range of 0.05–1.0 µg L^?1, and the method quantification limits (MQLs) for ultrapure water were within the range of 0.3–15 ng L^?1. All samples were extracted using Oasis© hydrophilic–lipophilic balanced cartridges with optimised sample size and extraction conditions. Good accuracy was demonstrated, with solid-phase extraction recoveries above 80% for most PPCPs. In environmental matrices, the MQLs for river water, sewage treatment plant (STP) effluent and STP influent were 4–25, 10–153 and 38–386.5, respectively. The method was successfully applied to investigate occurrences of persistent PPCPs in Malaysian river and sewage samples.     

Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.     

Syntheses and properties of fluorinated polyamides and poly(amide imide)s based on 9,9-bis[4-(4-amino-2-trifluromethylphenoxy)phenyl]fluroene, aromatic dicarboxylic acids, and various monotrimellitimides and bistrimellitimides

A diamine, 9,9-bis[4-(4-amino-2-trifluromethylphenoxy)phenyl]fluroene (I) containing the CF₃ group, was prepared from 9,9-bis(4-hydroxyphenyl)fluorene and 2-chloro-5-nitrobenzotrifluoride. The imide-containing diacids (V _a-j and VI _a,b) were prepared by condensation reaction of amino acids, aromatic diamines, and trimellitic anhydride. Then, a series of soluble fluorinated polyamides (VII _a-e) and poly(amide imide)s (VIII _a-j and X _a,b) were synthesized from diamine (I) with various aromatic diacids II _a-h and the imide-containing diacids (V _a-j and VI _a,b) via direct polycondensation with triphenyl phosphate and pyridine. All polymers showed excellent solubility in amide-type solvents such as N-dimethylforamide and can also be dissolved in pyridine, m-cresol, and tetrahydrofuran. Polymers afford transparent and tough films by solvent casting. The glass transition temperature of these polymers were in the range of 278–366°C, and the poly(amide imide)s had better thermal stability than polyamides. In comparison with the isomeric IX _a-d, VIII _a-d showed a lighter color with lower b* (yellowness index) values than the corresponding IX series.