Acetyl Derivatives Research Articles

A comparison between Hydrochloric acid and Trifluoroacetic acid in hydrolysis method of exopolysaccharide from Ophiocordyceps sinensis in Monosaccharide composition analysis by GC-FID

The monosaccharide composition is one of the crucial factors affecting the bioactivity of exopolysaccharide (EPS) in Cordyceps species. Therefore, many scientists have studied, analyzed monosaccharide composition and structure of EPS from Cordyceps species, especially Ophiocordyceps sinensis (O. sinensis). This study aimed to compare hydrochloric acid (HCl) with trifluoroacetic acid (TFA) in the EPS hydrolysis process in monosaccharide composition analysis by Gas Chromatography with Flame-Ionization Detection (GC-FID). The hydrolysis is a crucial step in forming the acetyl derivative, which helps the GC-FID technique to have good results in monosaccharide composition analysis. The results showed that hydrolysis with HCl gave a higher hydrolysis efficiency and was more suitable than hydrolysis by TFA in pretreatment to EPS for GC-FID. Hydrolysis results were analyzed through thin-layer chromatography and high-performance liquid chromatography (HPLC), then Acetyl derivatives were produced and finally analyzed by GC-FID to determine the monosaccharide composition of EPS. For EPS hydrolyzed by HCl, the analytical results presented that this sample had 6 kinds of monosaccharides, including rhamnose, arabinose, xylose, mannose, glucose, and galactose; the most monosaccharide was glucose. The EPS hydrolyzed by TFA only detected three kinds of monosaccharides, including mannose, arabinose, and galactose, mainly mannose. The study has set a foundation for further analysis of monosaccharide composition and structure of EPS from O. sinensis.

Synthesis of hybrid perillyl‐4H‐pyrans. Cytotoxicity evaluation against hepatocellular carcinoma HepG2/C3A cell line

AbstractA series of 15 new hybrid perillyl‐4H‐pyrans compounds was straightforwardly synthesized by a strategy combining the multicomponent reaction and the copper‐catalyzed alkyne‐azide cycloaddition (CuAAC). The 2‐amino‐4H‐pyrans‐3‐carbonitrile containing the alkyne moiety was prepared via multicomponent reaction between 1,3‐dicarbonyl, a propargyloxy aromatic aldehyde and malononitrile or ethyl α‐cyanoacetate. The alkyne derivative was sequentially reacted with the perillyl azide component through the copper‐catalyzed [3+2] Huisgen cycloaddition reaction. The antiproliferative activity of hybrid compounds were evaluated against the human hepatoma HepG2/C3A cell line.

Cytotoxicity of the Sesquiterpene Lactone Spiciformin and Its Acetyl Derivative against the Human Leukemia Cell Lines U-937 and HL-60.

Spiciformin (1) is a sesquiterpene lactone with a germacrane skeleton that is found in two Tanacetum species endemic to the Canary Islands. In this study, the cytotoxicities of 1 and its acetyl derivative (2) were evaluated against human tumor cells. These sesquiterpene lactones were cytotoxic against human acute myeloid leukemia (U-937 and HL-60) cells, even in cells over-expressing the pro-survival protein Bcl-2, but melanoma (SK-MEL-1) and human mononuclear cells isolated from blood of healthy donors were more resistant. Both compounds are apoptotic inducers in human leukemia U-937 cells. Cell death was mediated by the processing and activation of initiator and effector caspases and the cleavage of poly(ADP-ribose) polymerase, and it was blocked by a broad-spectrum caspase inhibitor and (in the case of sesquiterpene lactone 2) by the selective caspase-3/7, -8, and -9 inhibitors. In addition, certainly in the case of compound 2, this was found to be associated with a decrease in mitochondrial membrane potential, downregulation of the anti-apoptotic protein Bcl-2, activation of the mitogen-activated protein kinases signaling pathway, and generation of reactive oxygen species. It will, therefore, be relevant to continue characterization of this class of compounds.

Azides and Porphyrinoids: Synthetic Approaches and Applications. Part 2-Azides, Phthalocyanines, Subphthalocyanines and Porphyrazines.

The reaction between organic azides and alkyne derivatives via the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) is an efficient strategy to combine phthalocyanines and analogues with different materials. As examples of such materials, it can be considered the following ones: graphene oxide, carbon nanotubes, silica nanoparticles, gold nanoparticles, and quantum dots. This approach is also being relevant to conjugate phthalocyanines with carbohydrates and to obtain new sophisticated molecules; in such way, new systems with significant potential applications become available. This review highlights recent developments on the synthesis of phthalocyanine, subphthalocyanine, and porphyrazine derivatives where CuAAC reactions are the key synthetic step.

Polyphenols and Sesquiterpene Lactones from Artichoke Heads: Modulation of Starch Digestion, Gut Bioaccessibility, and Bioavailability following In Vitro Digestion and Large Intestine Fermentation.

Artichoke is a relevant source of health-promoting compounds such as polyphenols and sesquiterpene lactones. In this study, the bioaccessibility and gut bioavailability of artichoke constituents were evaluated by combining in vitro digestion and large intestine fermentation, metabolomics, and Caco-2 human intestinal cells model. Moreover, the ability of artichoke polyphenols to modulate the in vitro starch digestibility was also explored. An untargeted metabolomic approach based on liquid chromatography quadrupole-time-of-flight (UHPLC/QTOF) mass spectrometry coupled with multivariate statistics was used to comprehensively screen the phytochemical composition of raw, digested, and fermented artichoke. Overall, a large abundance of phenolic acids and sesquiterpene lactones was detected, being 13.77 and 11.99 mg·g−1, respectively. After 20 h of in vitro large intestine fermentation, a decrease in polyphenols and sesquiterpene lactones content was observed. The most abundant compounds characterizing the raw material (i.e., chlorogenic acid and cynaropicrin equivalents) showed an average % bioaccessibility of 1.6%. The highest % bioaccessibility values were recorded for flavonoids such as anthocyanin and flavone equivalents (on average, 13.6%). However, the relatively high bioavailability values recorded for flavonols, phenolic acids, and sesquiterpene lactones (from 71.6% up to 82.4%) demonstrated that these compounds are able to be transported through the Caco-2 monolayer. The phenolic compounds having the highest permeation rates through the Caco-2 model included low molecular weight phenolics such as tyrosol and 4-ethylcatechol; the isoflavonoids 3′-O-methylviolanone, equol 4′-O-glucuronide, and hydroxyisoflavone; together with the methyl and acetyl derivatives of glycosylated anthocyanins. Therefore, although human in vivo confirmatory trials are deemed possible, current findings provide insights into the mechanistic effects underlying artichoke polyphenols and sesquiterpenoids bioavailability following gastrointestinal and large intestine processes.

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons.

A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and alkene derivatives. Because an alkyne undergoes addition reaction at a C–C triple bond or cross-coupling at a terminal C–H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C–C multiple bonds. In this report, we found that the reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst. Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C–H coupling to produce indolinone derivative 5.

Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A

Neolignan licarin A (1) was isolated from leaves of Nectandra oppositifolia (Lauraceae) and displayed activity against trypomastigote forms of the etiologic agent of American trypanosomiasis, Trypanosoma cruzi. Aiming for the establishment of SAR, five different compounds (1a – 1e) were prepared and tested against T. cruzi. The 2-allyl derivative of licarin A (1d) exhibited higher activity against trypomastigotes of T. cruzi (IC50 = 5.0 μM and SI = 9.0), while its heterocyclic derivative 1e displayed IC50 of 10.5 μM and reduced toxicity against NCTC cells (SI > 19.0). However, these compounds presented limited oral bioavailability estimation (<85%, Papp <1.0 × 10−6 cm/s) in parallel artificial membrane permeability assays (PAMPA) due to excessive lipophilicity. Based on these results, different simplified structures of licarin A were designed: vanillin (2), vanillyl alcohol (3), isoeugenol (4), and eugenol (5), as well as its corresponding methyl (a), acetyl (b), O-allyl (c), and C-allyl (d) analogues. Vanillin (2) and its acetyl derivative (2b) displayed expressive activity against intracellular amastigotes of T. cruzi with IC50 values of 5.5 and 5.6 μM, respectively, and reduced toxicity against NCTC cells (CC50 > 200 μM). In addition, these simplified analogues showed a better permeability profile (Papp > 1.0 × 10−6 cm/s) on PAMPA models, resulting in improved drug-likeness. Vanillyl alcohol acetyl derivative (3b) and isoeugenol methyl derivative (4a) displayed activity against the extracellular forms of T. cruzi (trypomastigotes) with IC50 values of 5.1 and 8.8 μM respectively. Based on these results, compounds with higher selectivity index against extracellular forms of the parasite (1d, 1e, 3d, and 4a) were selected for a mechanism of action study. After a short incubation period (1 h) all compounds increased the reactive oxygen species (ROS) levels of trypomastigotes, suggesting cellular oxidative stress. The ATP levels were increased after two hours of incubation, possibly involving a high energy expenditure of the parasite to control the homeostasis. Except for compound 4a, all compounds induced hyperpolarization of mitochondrial membrane potential, demonstrating a mitochondrial imbalance. Considering the unique mitochondria apparatus of T. cruzi and the lethal alterations induced by structurally based on licarin A, these compounds are interesting hits for future drug discovery studies in Chagas disease.

Bioorthogonal Phosphorogenic Rhenium(I) Polypyridine Sydnone Complexes for Specific Lysosome Labeling.

Many novel bioorthogonal reactions have been developed for labeling, such as the strain-promoted sydnone-alkyne cycloaddition (SPSAC), but sydnone-based probes with phosphorogenicity (i. e., phosphorescence turn-on upon reaction) have not been investigated to date. Herein, we report the synthesis, characterization, and photophysical properties of rhenium(I) polypyridine complexes containing a sydnone moiety as bioorthogonal phosphorogenic probes. Their reactions with strained alkyne derivatives and the associated photophysical changes were examined. Upon SPSAC with bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH), the complexes exhibited emission enhancement in the range of 8.8 to 17.3. Importantly, conjugation of the complexes with BCN-modified bovine serum albumin (BCN-BSA) led to the increase in emission enhancement to as high as 38.9 and extended lifetimes in the range of 1.80 to 4.71 μs. Additionally, the bioorthogonal ligation of one of the complexes with a morpholine derivative was shown to induce specific lysosomal labeling in live cells; colocalization studies with LysoTracker Deep Red indicated a Pearson's coefficient of 0.83.

Synthesis and Application of Tetrafluoroethylene (CF2CF2)-Containing Acetylene Derivatives

On treating 1,3,4-tribromo-1,1,2,2-tetrafluorobutane, readily prepared from commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene, with 3.3 equivalents of LHMDS at 0 °C in THF, the corresponding lithium acetylide could be prepared quantitatively. The acetylide reacted well with various aldehydes, ketones, or chlorosilanes to give the corresponding acetylene derivatives in high yields. It was also found that various iodoarenes could participate in the cross-coupling reaction with the zinc acetylide, readily prepared from the lithium acetylide and ZnCl2·TMEDA complex, in the presence of Pd(PPh3)4 to bring about the adducts in high yields. Thus-obtained acetylene derivatives underwent smooth Diels–Alder reaction with various 1,3-dienes to afford the corresponding 1,4- or 1,3-cyclohexadiene derivatives. In addition, it was revealed that the oxidative aromatization of the resulting cyclohexadiene derivatives with DDQ took place very smoothly, providing the multi-substituted benzene derivatives having a tetrafluoro­ethylene group.

Organic Transformations Using Electron-Deficient Boron Compounds

The molecular structures and chemical reactivity of boron compounds are characterized by the electron deficiency and low electronegativity of boron. Based on simple molecular design strategy taking advantage of the unique properties of boron, we have developed new chemical species and new organic transformations. This article describes our recent studies of (i) a two-coordinate boron cation (borinium ion) and (ii) a 9-borafluorene-mediated benzannulation reaction of alkyne derivatives. In the former, we successfully isolated a diarylborinium ion (Mes2B+), which had been considered impossible to be isolated as a stable species without introducing particular electron-donating groups to boron. We found several unique small-molecule activation reactions mediated by Mes2B+ such as C=O double bond cleavage of CO2. Moreover, we revealed that Mes2B+ serves as an excellent hole-doping reagent for carbon nanotube, graphene, and transition metal dichalcogenide. In the latter topic, we discovered a new efficient boron-mediated benzannulation reaction of alkyne derivatives, which enables the synthesis of a wide variety of extended π-conjugated molecules and polymers. The boron compounds used in these studies are simple but enable powerful organic transformations.

FUNDAMENTAL AND APPLIED ASPECTS OF THE CHEMISTRY OF ACETYLENYLQUINONES

In addition to the reported synthetic routes for the acetylene derivatives of quinones, a detailed analysis of the fundamental chemical, physicochemical, and biological properties of this class of compounds is presented herein. The advantages of Pd- and Cu-catalyzed cross-coupling of terminal alkynes with iodarenes via the Sonogashira reaction to produce new acetylenylquinones with predetermined properties are examined. Here, combining quinoid and acetylene residues into one molecule gives the resulting compounds chemical specificity, as demonstrated by several reported examples of non-trivial transformations. In particular, the presence of the quinoid cycle significantly increases the electrophilicity of the triple bond and determines the range of transformation possibilities. Moreover, acetylenylquinones have heightened sensitivity to both external (such as the reaction temperature and the nature of the solvent) and internal (e.g., the structure of substituents in the nucleus and the acetylene fragment) factors. For example, regioselective cleavage of a strong triple bond under the action of amines is possible in the absence of a metal catalyst. Peri-substituted acetylenyl-9,10-anthraquinones are most suited for the synthetic route because of the proximity of the acetylene and carbonyl groups. Mechanisms of reactions of selective alkynylquinones are described.

FUNDAMENTAL AND APPLIED ASPECTS OF THE CHEMISTRY OF ACETYLENYLQUINONES

In addition to the reported synthetic routes for the acetylene derivatives of quinones, a detailed analysis of the fundamental chemical, physicochemical, and biological properties of this class of compounds is presented herein. The advantages of Pd- and Cu-catalyzed cross-coupling of terminal alkynes with iodarenes via the Sonogashira reaction to produce new acetylenylquinones with predetermined properties are examined. Here, combining quinoid and acetylene residues into one molecule gives the resulting compounds chemical specificity, as demonstrated by several reported examples of non-trivial transformations. In particular, the presence of the quinoid cycle significantly increases the electrophilicity of the triple bond and determines the range of transformation possibilities. Moreover, acetylenylquinones have heightened sensitivity to both external (such as the reaction temperature and the nature of the solvent) and internal (e.g., the structure of substituents in the nucleus and the acetylene fragment) factors. For example, regioselective cleavage of a strong triple bond under the action of amines is possible in the absence of a metal catalyst. Peri-substituted acetylenyl-9,10-anthraquinones are most suited for the synthetic route because of the proximity of the acetylene and carbonyl groups. Mechanisms of reactions of selective alkynylquinones are described.

On the nature of the interaction of copper hydride and halide with substituted ethylene and acetylene.

The association of Cu-X (X = -H, -Cl, and -F) with H2CCHCHmYn and HCCCHmYn (Y = -Cl, -F, -OH, -CH3) has been studied at a high level of theory. The density functional theory (DFT) at B3LYP/6-311G(d,p)//B3LYP/6-311 + G(3df,2p) level has been chosen to calculate the structure and the relative stability of 24 different complexes. The interaction of Cu-F with the derivatives of ethylene and acetylene was found very strong, with interaction energies close to those of conventional covalent bonds. In all complexes, the most stable structure was found when Cu-X is positioned on the unsaturated CC bond, forming a three-membered ring that leads to longer CC bond distances. Both ethylene and acetylene complexes show similar trends of interaction energies with respect to the same moiety. All electronic indexes analyzed by means of the QTAIM, ELF, and NBO formalisms indicate that the strength of the interaction should increase with the number of withdrawing substituents in both series of compounds. Graphical abstractThe p-Interaction of ethylene and acetylene derivative with fluoride copper. The ELF graphs and its 2D projection show the disynaptic basins of the electrostatic binding.

PH‐adjusted solvent extraction and reversed‐phase HPLC quantification of isoflavones from soybean (Glycine max (L.) Merr.)

Soybeans, Glycine max (L.) Merr., are among the most important food crops worldwide. Isoflavones are major bioactive phytochemicals in soybeans, and have a variety of health benefits, including antioxidative, antiatherosclerotic, antiinflammatory, and weak estrogen-like effects. The isoflavone content and composition of soybeans vary according to the cultivar and the extraction solvent conditions. Therefore, we investigated the effects of three different solvent pHs (1.0, 5.5, and 10.0) on the isoflavone, total phenolic, and total flavonoid contents and antioxidant capacities of eight soybean cultivars developed in Korea. Twelve isoflavones in soybeans were efficiently separated and identified on a reversed-phase high-performance liquid chromatography (HPLC) system. The percentage distribution of isoflavones measured by HPLC in the eight soybean cultivars at various extraction pHs decreased as follows: malonyl isoflavones (67.2% to 81.3%) > isoflavone glucosides (16.2% to 29.0%; as nonacylated form) > acetyl isoflavones (1.6% to 5.9%). The highest contents of isoflavone glucosides, malonyl derivatives, and acetyl derivatives were extracted at solvent pHs of 10.0, 1.0, and 5.5, respectively. The solvent extraction at pH 1.0 yielded a lower total isoflavone content than those at pHs 5.5 and 10.0. However, the highest total phenolic and flavonoid contents were extracted from soybeans at pH 1.0. Soybeans extracted at pH 10.0 displayed the highest antioxidant capacities in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay. Taken together, these results suggest that proper solvent pH adjustment is needed to maximize the extraction of targeted forms of isoflavones from soybeans. PRACTICAL APPLICATION: Soybeans contain a variety of bioactive compounds, including isoflavones, which function as antioxidants and weak phytoestrogens. Chemical and instrumental analyses can facilitate the selection of soybean cultivars with high amounts of isoflavones for soybean breeding and isoflavone-enriched product development. Proper solvent pH adjustment allows for the efficient extraction of high amounts of targeted isoflavone subgroups (acetyl and malonyl forms) from soybeans for functional food products.

A-type doubly linked proanthocyanidin trimer and other metabolites from Canthium venosum fruits, and their biological activities

Phytochemical investigation of Canthium venosum fruits led to the isolation of a new doubly linked A-type proanthocyanidin trimer: epicatechin-(2β→O→7, 4β →8)-catechin-(5→O→2β, 6→4β)-epicatechin [venosumtannin A-1 (1)], along with twenty known compounds 2-21. Allyl (9a) and acetyl (9b) derivatives of 9 were prepared. The structures of compounds were established using comprehensive spectroscopic analysis including 1D NMR, 2D NMR (COSY, HMQC, HMBC, and NOESY) and circular dichroism (CD), and by comparison with the corresponding literature data. The antioxidant, cytotoxic, acetylcholinesterase and antibacterial activities of some of the isolated compounds were investigated. In the acetylcholinesterase inhibitory activity test, compounds 2 and 9 (IC50: 0.03 ± 1.22 × 10−3 and 0.04 ± 1.23 × 10−3μM) were more active than the references (eserine and tacrine; IC50: 0.77 ± 1.84 × 10−3 and 0.15 ± 1.04 × 10−3 μM respectively).

Electrochemical synthesis of α,α-dihaloacetophenones from terminal alkyne derivatives

By virtue of electrochemistry, a series of α,α-dihaloacetophenones were easily obtained with good to excellent yields. This electrochemical procedure was taken in a divided cell with constant current in aqueous media. The reaction can be carried out smoothly at room temperature under metal and oxidant free condition, which provides an eco-friendly synthesis for the α,α-dihaloacetophenone derivatives.

Pharmacological and Cellular Significance of Triazole-Surrogated Compounds

: Heterocyclic compounds have been at the hierarchy position in academia, and industrial arena, particularly the compounds containing triazole-core are found to be potent with a broad range of biological activities. The resistance of triazole ring towards chemical (acid and base) hydrolysis, oxidative and reductive reaction conditions, metabolic degradation and its higher aromatic stabilization energy makes it a better heterocyclic core as therapeutic agents. These triazole-linked compounds are used for clinical purposes for antifungal, anti-mycobacterium, anticancer, anti-migraine and antidepressant drugs. Triazole scaffolds are also found to act as a spacer for the sake of covalent attachment of the high molecular weight bio-macromolecules with an experimental building blocks to explore structure-function relationships. Herein, several methods and strategies for the synthesis of compounds with 1,2,3-triazole moiety exploring Hüisgen, Meldal and Sharpless 1,3-dipolar cycloaddition reaction between azide and alkyne derivatives have been deliberated for a series of representative compounds. Moreover, this review article highlights in-depth applications of the [3+2]-cycloaddition reaction for the advances of triazole-containing antibacterial as well as metabolic labelling agents for the in vitro and in vivo studies on cellular level.

Occurrence and Co-Occurrence of Mycotoxins in Cereal-Based Feed and Food.

Dietary (co)-exposure to mycotoxins is associated with human and animal health concerns as well as economic losses. This study aims to give a data-based insight from the scientific literature on the (co-)occurrence of mycotoxins (i.e., parent and modified forms) in European core cereals, and to estimate potential patterns of co-exposure in humans and animals. Mycotoxins were mainly reported in wheat and maize showing the highest concentrations of fumonisins (FBs), deoxynivalenol (DON), aflatoxins (AFs), and zearalenone (ZEN). The maximum concentrations of FB1+FB2 were reported in maize both in feed and food and were above legal maximum levels (MLs). Similar results were observed in DON-food, whose max concentrations in wheat, barley, maize, and oat exceeded the MLs. Co-occurrence was reported in 54.9% of total records, meaning that they were co-contaminated with at least two mycotoxins. In the context of parental mycotoxins, co-occurrence of DON was frequently observed with FBs in maize and ZEN in wheat; DON + NIV and DON + T2/HT2 were frequently reported in barley and oat, respectively. Apart from the occurrence of ZEN and its phase I and phase II modified forms, only a limited number of quantified data were available for other modified forms; i.e., mainly the acetyl derivatives of DON. Data gaps are highlighted together with the need for monitoring studies on multiple mycotoxins to identify co-occurrence patterns for parent mycotoxins, metabolites, and their modified forms.

Chiral information harvesting in helical poly(acetylene) derivatives using oligo(p-phenyleneethynylene)s as spacers.

A chiral harvesting transmission mechanism is described in poly(acetylene)s bearing oligo(p-phenyleneethynylene)s (OPEs) used as rigid achiral spacers and derivatized with chiral pendant groups. The chiral moieties induce a positive or negative tilting degree in the stacking of OPE units along the polymer structure, which is further harvested by the polyene backbone adopting either a P or M helix.

Synthesis and Reactivity of 2-(Thiophen-2-yl)[1,3]thiazolo[4,5-f]quinoline

The condensation of quinolin-5-amine with thiophene-2-carbonyl chloride in propan-2-ol gave N-(quinolin-5-yl)thiophene-2-carboxamide. Treatment of the latter with excess diphosphorus pentasulfide in anhydrous pyridine afforded the corresponding thioamide which was oxidized with potassium hexacyanoferrate(III) in alkaline medium to obtain 2-(thiophen-2-yl)[1,3]thiazolo[4,5-f]quinoline. The oxidation product was subjected to electrophilic substitution reactions, in particular nitration, sulfonation, bromination, formylation, and acylation, which led to the formation of the corresponding derivatives substituted exclusively at the 5-position of the thiophene ring. Acylation of 2-(thiophen-2-yl)[1,3]thiazolo[4,5-f]quinoline with acetic anhydride produced a mixture of acetyl and acetoacetyl derivatives.