Glycosyl Derivatives Research Articles

Electrochemical Ferrier Rearrangement of Glycals.

The Ferrier rearrangement (FR) is a well-documented reaction that relies on strong acids or oxidants to convert glycals into unsaturated glycosyl derivatives. In this work, we introduce an electrochemical variant of the FR, offering a broad substrate compatibility. Various nucleophiles and glycal derivatives afford 2,3-unsaturated glycosyl derivatives in high yields with excellent diastereoselectivities. This sustainable method promises to expand the electrochemistry applications in sugar chemistry.

Synthesis and cytotoxic evaluation of glycosyl derivatives of icaritin

A series of glycosyl alkyl/triazol-linked icaritin derivatives have been designed and synthesised. The target glycosyl derivatives were evaluated for their anticancer activity against three human cancer cell lines. The results of preliminary anticancer tests in vitro revealed that mannose derivatives 10a–10c (100 μM) with different aliphatic chain lengths exhibited increased cytotoxicity against HepG2 and SK-OV-3 cells compared with the parent compound icaritin. The data indicated that the kind of glycosyl groups and linkers affected the anticancer potency significantly. The ADME analysis of derivatives 10a–10c was also performed.

Dereplication of calystegines in food plants and wild Solanum Brazilian fruits

Calystegines are potent glycosidase inhibitors with therapeutic potential and are constituents of food and feed with potential toxic effects. This study aims to target calystegines and other nitrogenous substances in food plants. Hydroalcoholic extracts from Solanum tuberosum, Ipomoea batatas, S. lycocarpum, and fruit from S. lycopersicum, S. aethiopicum, S. paniculatum, S. crinitum, and S. acanthodes were analyzed by liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) using an acidic HILIC column. The dereplication approach included data processing using MZMine2, FBMN-GNPS, and structure elucidation and interpretation of the organized data. The calystegines A3, A5, B2, and C1 were identified, and several potential new calystegine analogues: three may correspond to new calystegines of the A-group, one glycosyl derivative of calystegine A3, and two glycosyl derivatives of the B-group. These findings help to direct the search for new calystegines. In addition, the dereplication approach enabled the annotation of 22 other nitrogen compounds.

Site‐Selective Direct Intermolecular C(sp3)−H Alkylation of Saccharides and Switching of Reaction Sites by Changing Photocatalysts

AbstractWe developed a site‐selective intermolecular C(sp3)−H alkylation of saccharides with electron‐deficient alkenes using photocatalysis by anthraquinone and tetrabutylammonium decatungstate (TBADT). The main reaction site of anthraquinone‐catalyzed C(sp3)−H alkylation is determined by the weakness of the C−H bond. The reaction site can be switched by changing the photocatalyst to TBADT, and the site‐selectivity is controlled by the steric hindrance between the bulkier TBADT photocatalyst and the substituents of the saccharides. The reaction is compatible with several electron‐deficient alkenes and saccharides, and provides C‐saccharides in good yields. Furthermore, the monoalkylated product was obtained in excellent yield, even on the gram scale, under TBADT photocatalysis. Applicability was demonstrated by site‐selective C(sp3)−H alkylation of glycosyl derivatives. The reactions proceed via a site‐selective hydrogen atom transfer between the photocatalyst and saccharide, and the generated carbon radical reacts with an electron‐deficient alkene to give alkylated products.

The Development of DNA-Compatible S-Glycosyl Transformations.

In this study, we revealed two distinct S-glycosyl transformations in a DNA-encoded library (DEL)-compatible environment. The first approach involves 2-chloro-1,3-dimethylimidazolidinium chloride (DMC)-mediated S-glycosylation, which is facilitated by the coupling of unprotected sugar units with the thiol residue of the DNA-linked compounds. However, this methodology falls short of the requirement for DEL construction due to its limited substrate scope. We further investigated a photoinduced DNA-compatible S-glycosyl transformation through a radical process. In this alternative approach, allyl sugar sulfones serve as sugar donors and are conjugated to DNA-linked compounds upon irradiation with green light. Encouragingly, this on-DNA glycosyl chemistry demonstrated excellent compatibility with functional groups presented in both sugar units and peptides, affording the desired DNA-linked glycosyl derivatives with good to excellent conversions. This pioneering DNA-compatible S-glycosyl transformation represents a valuable tool, facilitating the preparation of glycosyl DELs and offering avenues for the exploration of sugar-incorporated delivery systems.

Impact of molecular interactions between hydrophilic phytosterol glycosyl derivatives and bile salts on the micellar solubility of cholesterol

Hydrophilic phytosterol glycosyl derivatives are synthetic phytosterol analogues by coupling with the glycosyl moiety to improve the water solubility and bioaccessibility of free phytosterols. The aim of this study is to clarify the molecular interaction of phytosterol glycosyl derivatives with bile salts and the consequent impact on cholesterol solubilization. Sharp nonlinear decrease in the micellar solubility of cholesterol and accompanying changes in particle size, zeta potential and microtopography of mixed micelles were observed when phytosterol glycosyl derivatives were introduced in cholesterol-loaded bile salt micelles. These results suggested that β-sitosterol glycosyl derivatives molecules indeed participated in the formation of mixed micelles. Further, nuclear magnetic resonance showed that the structural change of mixed micelles was caused by the insertion of β-sitosterol glycosyl derivatives via hydrogen bonds with sodium taurocholate, which resulted in the low cholesterol solubilization. Moreover, the hydrogen-bond interactions were apparently influenced by the glycosyl moiety of β-sitosterol glycosyl derivatives. These molecular mechanisms may contribute to the development of cholesterol-absorption inhibitors.

Nutrichemical alterations in different fractions of multiple-harvest alfalfa (Medicago sativa L.) green biomass fortified with various selenium forms

Background and AimsWet processed alfalfa-based products can provide high-quality concentrated protein, also contain nutrients and phytochemicals. Agronomic fortification can increase selenium (Se) incorporation into green biomass. For this reason, the aim was to investigate how different forms of Se are incorporated into the green biomass of multiple-harvest alfalfa and how they affect the chemical quality of the processed product candidates.MethodsIn this research, alfalfa was enriched with three forms of selenium at different concentrations [selenate (Se(VI)); selenite (Se(IV)); and red elemental Se (Se0)]. The fortified green biomass was fractionated into leaf protein concentrate (LPC), fiber and phytoserum, and changes in selenium content and speciation, protein and phytochemical composition were determined.ResultsTotal Se content in alfalfa fractions drastically reduced within the four consecutive harvests, particularly for Se(VI) and Se(IV) forms, and significantly varied according to the Se treatments. Selenomethionine (SeMet) was the predominant organic Se species in LPC (35.7–246.0 µg g −1 DW) and fiber (9.0- 47.7 µg g −1 DW) fractions. Se-fortification induced considerable changes in the crude protein of LPC, which varied between 29—45 (m/m)%. Phytochemical composition markedly varied among Se-treatments. Besides several flavonoids, aglycones and glycosyl derivatives, apigenin glucuronide, and apigenin were the most abundant with a concentration up to 170.85 µg g −1 DW. Medicagenic acid concentration was below 1.86 µg g −1 DW in LPC.ConclusionsSe-enhanced alfalfa green biomass could provide functional products, such as LPC, for human and animal consumption with enhanced nutritional value, including Se, protein, and phytochemical contents.

Integrative analysis of sensory evaluation and non-targeted metabolomics to unravel tobacco leaf metabolites associated with sensory quality of heated tobacco.

Heated tobacco (Nicotiana tabacum L.) products are heating tobacco plug at a temperature of 350°C and produce different emissions in aerosol and sensory perceptions of tobacco leaf compared with combustible tobacco. Previous study assessed different tobacco varieties in heated tobacco for sensory quality and analyzed the links between sensory scores of the final products and certain chemical classes in tobacco leaf. However, contribution of individual metabolites to sensory quality of heated tobacco remains largely open for investigation. In present study, five tobacco varieties were evaluated as heated tobacco for sensory quality by an expert panel and the volatile and non-volatile metabolites were analyzed by non-targeted metabolomics profiling. The five tobacco varieties had distinct sensory qualities and can be classified into higher and lower sensory rating classes. Principle component analysis and hierarchical cluster analysis showed that leaf volatile and non-volatile metabolome annotated were grouped and clustered by sensory ratings of heated tobacco. Orthogonal projections to latent structures discriminant analysis followed by variable importance in projection and fold-change analysis revealed 13 volatiles and 345 non-volatiles able to discriminate the tobacco varieties with higher and lower sensory ratings. Some compounds such as β-damascenone, scopoletin, chlorogenic acids, neochlorogenic acids, and flavonol glycosyl derivatives had strong contribution to the prediction of sensory quality of heated tobacco. Several lyso-phosphatidylcholine and lyso-phosphatidylethanolamine lipid species, and reducing and non-reducing sugar molecules were also positively related to sensory quality. Taken together, these discriminating volatile and non-volatile metabolites support the role of leaf metabolites in affecting the sensory quality of heated tobacco and provide new information on the types of leaf metabolites that can be used to predict applicability of tobacco varieties for heated tobacco products.

Efficient Synthesis and In Vitro Hypoglycemic Activity of Rare Apigenin Glycosylation Derivatives.

Apigenin is a natural flavonoid with significant biological activity, but poor solubility in water and low bioavailability limits its use in the food and pharmaceutical industries. In this paper, apigenin-7-O-β-(6″-O)-d-glucoside (AG) and apigenin-7-O-β-(6″-O-succinyl)-d-glucoside (SAG), rare apigenin glycosyl and succinyl derivatives formed by the organic solvent-tolerant bacteria Bacillus licheniformis WNJ02 were used in a 10.0% DMSO (v/v) system. The water solubility of SAG was 174 times that of apigenin, which solved the application problem. In the biotransformation reaction, the conversion rate of apigenin (1.0 g/L) was 100% at 24 h, and the yield of SAG was 94.2%. Molecular docking showed that the hypoglycemic activity of apigenin, apigenin-7-glucosides (AG), and SAG was mediated by binding with amino acids of α-glucosidase. The molecular docking results were verified by an in vitro anti-α-glucosidase assay and glucose consumption assay of active compounds. SAG had significant anti-α-glucosidase activity, with an IC50 of 0.485 mM and enhanced glucose consumption in HepG2 cells, which make it an excellent α-glucosidase inhibitor.

Evaluation of the Lysyl Oxidase-Like 2 (LOXL2) inhibitory activity of pimaranes and their glycosyl derivatives

Lysyl oxidase (LOX) and LOX-like 1-4 (LOXL 1-4) enzymes catalyze the cross-linking of elastin and collagen in the extracellular matrix, facilitating cell migration and invasion. The inhibition of these enzymes, particularly LOXL2, has been suggested as a therapeutic strategy to prevent breast cancer metastasis. In this work, new natural LOXL2 inhibitors were searched from Aeollanthus rydingianus, a medicinal plant rich in bioactive products. Five pimarane diterpenoids, two isolated from the plant and three derivatives, were tested. These compounds have been described for their bioactive properties such as anti-tumor, anti-inflammatory, analgesic, and antibacterial activities. In this regard, we intended to explore the mechanisms of these compounds by studying their effects on LOXL2 activity. Two pimarane diterpenoids showed a mild LOXL2 inhibitory activity as evaluated by an Amplex Ultra Red-based technique. The cytotoxicity of the most active compound was analyzed by the MTT assay in the MDA-MB-231 cell line, representative of triple-negative breast cancer. This compound decreased cell viability as single agent and increased the cytotoxic effect of doxorubicin. Its glycoconjugate was considerably more toxic, likely due to a higher uptake by cancer cells. Keywords: breast cancer, lysyl oxidase-like 2, inhibitors, pimaranes, Aeollanthus rydingianus, MTT

Food flavonols: Nutraceuticals with complex health benefits and functionalities

Flavonols are one of the most promising class of bioactive compounds belonging to the broad family of the flavonoids, characterized by a unique set of features in their basic chemical skeleton and several specific substitutions in selected position of the rings A, B and C. This interesting class of phytochemicals includes compounds such as quercetin, kaempferol, myricetin, rhamnetin, morin, fisetin, galagin, azaleatin and their respective glycosyl derivatives. They have been identified in several foods and provide them great health benefits. This review updates and integrates, in a critical fashion, the current knowledge on flavonols as food sources, chemical features, structure-activity relationships, bioavailability and health benefits (from preclinical and clinical studies), focusing on both in vitro and in vivo reports. Dietary flavonols are bioavailable molecules in human with impressive health benefits (such as antioxidation, cardioprotection, antibacterial, antiviral and anticancer activity) and the process of metabolization also produces compounds with remarkable bioactivities just like the corresponding precursors. Their inclusion into human diet is highly recommended for their unquestionable health promoting properties, being excellent nutraceuticals as well as ingredients for good functional food. • Food flavonols are nutraceuticals with remarkable biological applications. • Basic skeleton of flavonols has characteristic features for their functionality. • Some foods in the human diet are very rich source of flavonols. • Flavonols have promising anticancer, antimicrobial, antioxidant and antiviral properties.

Insight into the Ferrier Rearrangement by Combining Flash Chemistry and Superacids

AbstractThe transformation of glycals into 2,3‐unsaturated glycosyl derivatives, reported by Ferrier in 1962, is supposed to involve an α,β unsaturated glycosyl cation, an elusive ionic species that has still to be observed experimentally. Herein, while combination of TfOH and flow conditions failed to observe this ionic species, its extended lifetime in superacid solutions allowed its characterization by NMR‐based structural analysis supported by DFT calculations. This allyloxycarbenium ion was further exploited in the Ferrier rearrangement to afford unsaturated nitrogen‐containing C‐aryl glycosides and C‐alkyl glycosides under superacid and flow conditions, respectively.

Insight into the Ferrier Rearrangement by Combining Flash Chemistry and Superacids.

The transformation of glycals into 2,3-unsaturated glycosyl derivatives, reported by Ferrier in 1962, is supposed to involve an α,β unsaturated glycosyl cation, an elusive ionic species that has still to be observed experimentally. Herein, while combination of TfOH and flow conditions failed to observe this ionic species, its extended lifetime in superacid solutions allowed its characterization by NMR-based structural analysis supported by DFT calculations. This allyloxycarbenium ion was further exploited in the Ferrier rearrangement to afford unsaturated nitrogen-containing C-aryl glycosides and C-alkyl glycosides under superacid and flow conditions, respectively.

Synthesis and Cytotoxic Property of Annonaceous Acetogenin Glycoconjugates.

BackgroundAnnonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated.MethodsIn order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay.ResultsNine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS).ConclusionThe conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.

The first synthesis of peracetyl glycosyl aurone derivatives and aurone glucosides

Aurones, a sub-class of the flavonoids with proven therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-α-D glucopyranosyl bromide in the presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB). The successful synthesis of aurone glycosides (33 examples) in 60–92% yield will benefit the synthesis of combinatorial libraries of glycosylated aurones for their biological study and comparison with non-glycosylated aurones.

Phenolic Fingerprinting, Antioxidant, and Deterrent Potentials of Persicaria maculosa Extracts.

Persicaria maculosa (Polygonaceae) (known as lady’s thumb) is an annual morphologically variable weed that is widely distributed in Chile. The purpose of this study was to investigate the antifeedant potential of methanolic (MeOH), ethanolic (EtOH), and dichloromethane (DCM) extracts from the aerial parts of this plant collected in the Valparaíso and Curicó provinces (Chile) and relate this activity to the antioxidant capacity and the presence of phenolic compounds in the extracts. A phenolic profile based on HPLC-ESI-MS/MS allowed the identification of 26 phenolic compounds, most of them glycosyl derivatives of isorhamnetin, quercetin, and kaempferol. In addition, the total phenolic content (TP), total flavonoids (TF), and antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion scavenging (O2−), ferric-reducing antioxidant power (FRAP), and cupric-reducing antioxidant capacity (CUPRAC) of the extracts are reported. The antifeedant potentials of the plant extracts were tested against Epilachna paenulata, Pseudaletia adultera, Macrosiphum euphorbiae, and Diaphorina citri insects for the first time. The activity against the aphid M. euphorbiae was significant for the DCM extracts of plants from Valparaíso and Curicó (settling % = 23% ± 4% and 23% ± 5%, respectively). The antifeedant activities against the beetle E. paenulata and the lepidoptera P. adultera were significant for Valparaíso extracts, especially when tested against E. Paenulata (IFP = 1.0 ± 0.0). Finally, the MeOH and EtOH extracts from Valparaíso plants reduced the diet consumption of the psilid D. citri (p < 0.05). The results showed that P. maculosa is a good source of flavonoids with some antioxidant capacities and has potential interest as botanical eco-friendly alternative with deterrent activity.

Chemical constituents of the aerial parts of Algerian Galium brunneum: Isolation of new hydroperoxy sterol glucosyl derivatives

Abstract The liposoluble extract of Galium brunneum aerial parts from North-eastern Algeria was chemically investigated. The EtOAc soluble portion contained a series of glycosyl cucurbitacins and sterols including three new glucosyl hydroperoxy sterols 1–3 among other phenolic components whereas the BuOH soluble fraction was dominated by glycosyl derivatives of flavonoids, iridoids and lignans, according to the chemistry reported in the literature for the genus Galium. The structure of new oxidized sterols 1–3 was determined by spectroscopic methods as well as by comparison with related known metabolites. Selected main compounds from both extracts, which revealed moderate antibacterial activities, were tested for their growth inhibitory properties against Gram-positive and Gram-negative bacteria. This is the first report of cucurbitacins in plants of genus Galium.

Naturally Occurring TPE-CA Maintains Gut Microbiota and Bile Acids Homeostasis via FXR Signaling Modulation of the Liver-Gut Axis.

Antibiotics-induced changes in intestinal flora (dysbiosis) may have various effects on the host. Dysbiosis is associated with numerous metabolites including bile acids, which are produced in the liver from cholesterol and metabolized in the gut by intestinal microbiota. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary flavanones and their glycosyl derivatives, including flavones, flavonols, polymethoxyflavones and coumarins, which exert positive health effects on the microbiota. The aim of this study is to elucidate the interplays between the intestinal microbiota and bile acids metabolism attributed to antibiotics. Mice were exposed to broad-spectrum antibiotics, such as ampicillin, streptomycin and clindamycin, for 14 days. This exposure resulted in reduced bacterial diversity and richness, and destroyed intestinal permeability. The homeostasis of bile acids was also affected. Subsequent TPE-CA administration, counteracted most of the dysbiosis, and reshaped intestinal permeability, these effects occurred via upregulation of zonula occludens 1 and occludin associated proteins and downregulation of serum endotoxin compared to the antibiotics group. TPE-CA maintained the homeostasis of bile acids via modulation of the liver–gut axis related farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15) pathway and FXR-targeted protein. Our findings indicated that TPE-CA exerted a protective effect on the restoration of intestinal microbiota composition, reshaped barrier integrity and maintained bile acid homeostasis via the liver–gut axis with antibiotics-induced dysbiosis.

Selective Synthesis and Molecular Structure of Novel Aminooxyglycosyl Derivatives Bearing Hydroxyphenyl Moieties

AbstractWe present the selective synthesis of novel aminooxy glycosyl derivatives bearing hydroxy phenyl moieties. A strict control over the anomeric and E/Z configurations has been achieved. The products obtained are α‐glycosides and the aromatic moiety substitute the Schiff's base trans to the O‐glycosidic bond. Single crystal X‐ray diffraction and NMR spectral data are reported and analysed.

Review] Synthesis of Glycosyl Derivatives and Glycomaterials Based on Direct Activation of Unprotected Sugars

Review] Synthesis of Glycosyl Derivatives and Glycomaterials Based on Direct Activation of Unprotected Sugars