C6-C3 Units Research Articles

Evaluation of antioxidant, antidiabetic and antiobesity potential of phenylpropanoids (PPs): Structure-activity relationship and insight into action mechanisms against dual digestive enzymes by comprehensive technologies

Phenylpropanoids (PPs), a group of natural compounds characterized by one or more C6-C3 units, have exhibited considerable potential in addressing metabolic disease. However, the comprehensive investigation on the relationship of compound structures and involved activity, along with the action mechanisms on the drug target is absent. This study aimed to evaluate the antioxidant and inhibitory activities of 16 PPs against two digestive enzymes, including α-glucosidase and pancreatic lipase, explore the structure–activity relationships and elucidate the mechanisms underlying enzyme inhibition. The findings revealed the similarities in the rules governing antioxidant and enzyme inhibitory activities of PPs. Specifically, the introduction of hydroxyl groups generally exerted positive effects on the activities, while the further methoxylation and glycosylation were observed to be unfavorable. Among the studied PPs, esculetin exhibited the most potent antioxidant activity and dual enzymes inhibition potential, displaying IC50 values of 0.017 and 0.0428 mM for DPPH and ABTS radicals scavenging, as well as 1.36 and 6.67 mM for α-glucosidase and lipase inhibition, respectively. Quantification analysis indicated esculetin bound on both α-glucosidase and lipase successfully by a mixed-type mode. Further analyses by UV–Vis, FT-IR, fluorescence spectra, surface hydrophobicity, SEM, and molecular docking elucidated that esculetin could bind on the catalytic or non-catalytic sites of enzymes to form complex, impacting the normal spatial conformation for hydrolyzing the substrate, thus exhibiting the weakened activity. These results may shed light on the utilization value of natural PPs for the management of hyperglycemia and hyperlipemia, and afford the theoretical basis for designing drugs with stronger inhibition against the dual digestive enzymes based on esculetin.

Stability and Bioaccessibility of Lignans in Food Products.

Lignans are a group of plant phenolic compounds with various technofunctional and health-promoting properties. They can be found in oilseeds (291.7-2513 mg/100 g), nuts, vegetables, fruits, and alcoholic and nonalcoholic drinks. The most common structural representative feature of lignans' backbone is a dimeric phenylpropanoid, which consists of two C6-C3 units joined by a central carbon. Compared to other phenolics, such as flavonoids, the literature on lignan stability and bioaccessibility is limited. This Mini-Review aims to present an overview of recent literature, draw connecting lines to the known regarding polyphenols, and suggest the main knowledge gaps. Processing methods and processing conditions influence the stability of lignans with several thermal treatments explored. Roasting, as a major studied processing step, displayed varying effects as a function of the lignan structure and matrix. The content of specific and even total lignans was shown to increase in some cases even after intense thermal treatment. Lignans were also reported to present a stabilizing effect against oxidation to oils when added externally. Different fermentation methods presented inconclusive outcomes on the content of lignans, likely stemming from the various matrices and microorganisms studied in a relatively limited pool of studies. The bioaccessibility of lignans in in vitro studies was usually low (from less than 1% in fermented flaxseed to 30% for microwaved artichokes). Yet, a clear conclusion regarding the digestive fate of lignans as a function of processing and structure cannot be currently suggested, and significant additional effort in this direction is needed.

Advances in the chemistry and pharmacological potential of coumarinolignans.

Coumarinolignans (CLs) are a group of non-conventional lignans having coumarins and phenyl propanes as two C6C3 units linked commonly through a dioxane bridge. The research findings during Jan 2008-May 2018 on this group of secondary metabolites describing their occurrence, structural characteristics, large-scale preparation, synthesis, derivatives, pharmacological activities, and structure-activity relationship are presented in this review. Around 38 CLs have been isolated from 40 plant species belonging to 20 different families during the review period. Reports on the syntheses of CL derivatives are also discussed. The majority of the reported CLs have shown potential anti-inflammatory activities, especially against pro-inflammatory cytokines. The other pharmacological effects exhibited by CLs such as hepatoprotective, anticancer, etc., are also covered in this review comprehending the lacunae in their development into drugs. This article is a continuation of our earlier work on coumarinolignans (Begum SA, Sahai M, Ray AB (2010) Non-conventional lignans: coumarinolignans, flavonolignans, and stilbenolignans. In: Kinghorn AD, Falk H, Kobayashi J (eds) Progress in the chemistry of organic natural products, Springer, Verlag/Wien, p 1-70).

Novel sesquilignan and lignan glycoside from the twigs and leaves of Illicium majus

A novel sesquilignan compound (1), possesing an unusual carbon skeleton of aryltetralin unit linked with a C6-C3 unit and a five-membered ring by a C-7″ and C-4 linkage pattern via an oxygen atom, and a new lignan glycoside (2) have been isolated from the twigs and leaves of Illicium majus. Their structures were determined by spectroscopic analysis and chemical methods. The absolute configurations of 1 and 2 are confirmed by observing the circular dichroism. At 10 μM, Compounds 1 and 2 showed in Vitro inhibitory activity against the release of β-glucuronidase in rat polymorphonuclear leukocytes induced by platelet-activating factor.

Magterpenoids A-C, Three Polycyclic Meroterpenoids with PTP1B Inhibitory Activity from the Bark of Magnolia officinalis var. biloba.

Magterpenoid A (1), possessing a rare 4,6,11-trioxatricyclo[5.3.1.01,5]undecane framework with an irregular monoterpenoid moiety, magterpenoid B (2), with an unprecedented 6/6/6/6 polycyclic skeleton, and magterpenoid C (3), a novel terpenoid quinone with a C6-C3 unit, were isolated from the bark of Magnolia officinalis var. biloba. Plausible biogenetic pathways of 1-3 are presented. Compounds 1 and 3 exhibited significant PTP1B inhibitory activities with IC50 values of 1.44 and 0.81 μM, respectively.

Pot‐Economical Synthesis of Hydroxylated Arylethenyl‐arylethynyl‐arenes through Sequential Decarboxylative Perkin–Sonogashira Reactions

AbstractA simple, economical and one‐pot protocol is developed for construction of multiple carbon–carbon bonds having C(sp2)−C(sp2) and C(sp2)−C(sp) hybridization, as these intriguing molecular architectures exhibit significant optoelectronic and medicinal properties. To this end, a sequential reaction is devised that allows one‐pot three‐component reactions of hydroxybenzaldehydes (C6–C1 unit), halo‐phenylacetic acids (C6–C2 unit) and arylacetylenes (C6–C3 unit) resulting in the formation of highly π‐conjugated complex arylethenyl‐arylethynyl‐arenes (C6–C2–C6–C2–C6 unit) bearing a hydroxy group via sequential Perkin condensation–decarboxylation–Sonogashira coupling in polyethylene glycol with microwave irradiation. The process avoids protection–deprotection manipulations, generates CO2 and H2O as by‐products and is successfully extended for the efficient construction of a wide series of novel aliphatic/alicyclic/(hetero)aromatic arylethenyl‐arylethynyl‐arenes with pendant hydroxy functionality, which could undergo further chemical modification to achieve target biological and physical properties.

Divergent Synthesis of Styryl–Cinnamate Hybrid Analogues Inspired by the Natural Product Salvianolic Acid F as a Premise To Investigate Their Anticancer Activity and Its Metabolomic Profiling

Protecting‐group‐free synthesis of hydroxylated styryl–cinnamate hybrids (C6–C2–C6–C3 unit), inspired by the natural product salvianolic acid F, was achieved by a step‐economical route involving sequential double C–C bond formation in one pot. The method involved multiple reactions (Perkin condensation/decarboxylation–Heck cross‐coupling reactions) by using simple precursors (i.e., hydroxylated benzaldehyde, arylacetic acid, and acrylic acid derivatives) in one pot and yielded the desired unnatural small hybrid molecules in varying yields of 35–65 % with E selectivity under microwave irradiation, whereas the reported conventional route for the synthesis of salvianolic acid F itself requires six steps with an overall yield of 10.0 % in addition to tedious separation of E/Z isomers that arise from a Wittig reaction. Apart from an economical synthesis and product diversity, we herein report the potential of some hybrid molecules with the catechol core to selectively inhibit glioma cells. The intrinsic mode of action of our lead molecule, involving caspase 6 and the quinonemethide pathway, is also reported on the basis of 1H NMR spectroscopy guided metabolomic profiling. We emphatically demonstrate the role of our hybrid molecules, analogues of salvianolic acid F, in forcing glioma cells towards apoptosis by specifically perturbing the concentration of glutathione along with that of caspase 6.

Biotechnological approaches for producing aryltetralin lignans from Linum species

The genus Linum includes more than 230 globally distributed species, which have attracted great interest as they grow rapidly and are already sources of commercially important products, e.g. flax and linseed oil. Furthermore, they contain lignans such as podophyllotoxin (PTOX), deoxypodophyllotoxin (a precursor of both PTOX and 6-methoxypodophyllotoxin, the latter via β-peltatin, and β-peltatin-A-methyl ether) and various derivatives. Lignans are natural compounds derived from two 8,8′-linked C6C3 (propylbenzene) units. PTOX is an aryltetralin-lignan with strong cytotoxic and antiviral activities. Thus, it is used as a starting material for producing various semisynthetic derivatives that are widely used in chemotherapy, such as etoposide, teniposide and etopophos. It is currently produced largely from Podophyllum hexandrum and P. peltatum, slow-growing endangered species of the Berberidaceae. Hence, the possibility of producing it from Linum, especially members of section Syllinum under either in vitro or ex vitro conditions is highly attractive. This review summarizes related research, focusing on in vitro production of aryltetralin lignans from various Linum species and possible biotechnological strategies to improve their production. The key pathways, enzymes and genes involved are highlighted and future challenges that must be met to allow viable, large-scale production of this anticancer drug lead are discussed.

Nanostructural assembly of cellulose, hemicellulose, and lignin in the middle layer of secondary wall of ginkgo tracheid

Physical, chemical, and biological properties of wood depend largely on the properties of cellulose, noncellulosic polysaccharides, and lignin, and their assembly mode in the cell wall. Information on the assembly mode in the main part of the ginkgo tracheid wall (middle layer of secondary wall, S2) was drawn from the combined results obtained by physical and chemical analyses of the mechanically isolated S2 and by observation under scanning electron microscopy. A schematic model was tentatively proposed as a basic assembly mode of cell wall polymers in the softwood tracheid as follows: a bundle of cellulose microfibrils (CMFs) consisting of about 430 cellulose chains is surrounded by bead-like tubular hemicellulose-lignin modules (HLM), which keep the CMF bundles equidistant from each other. The length of one tubular module along the CMF bundle is about 16 ± 2 nm, and the thickness at its side is about 3–4 nm. In S2, hemicelluloses are distributed in a longitudinal direction along the CMF bundle and in tangential and radial directions perpendicular to the CMF bundle so that they are aligned in the lamellae of tangential and radial directions with regard to the cell wall. One HLM contains about 7000 C6-C3 units of lignin, and 4000 hexose and 2000 pentose units of hemicellulose.

Isoflavone Daidzein: Chemistry and Bacterial Metabolism

Isoflavone daidzein is a phytoestrogen widely distributed in Leguminosae and is especially rich in the soybean. The C6-C3 (rings B and C) unit of isoflavones is derived from the phenylpropanoid pathway and the remaining C6 (ring A) unit is from the polyketide pathway. This unique carbon skeleton is the result of isomerization of the flavone catalyzed by the isoflavone synthase, a cytochrome P450 enzyme. The isoflavones daidzein and genistein are present in the plant mostly in the glucosylated forms. However, in the human intestine, the glycosidic linkage is broken, and the free form is uptaked into blood stream. The free form is further metabolized into various reduction products to end up at the equol, which is known to have the most potent estrogenic effect among the metabolites. Several human intestinal bacteria that can convert daidzein into equol have been described, and the study into the chemistry and biochemistry of the daizein reduction would be rewarding to the improvement of the human health.

Apteniols A—F, Oxyneolignans from the Leaves of Aptenia cordifolia

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

TMAH-pyrolysis – gas chromatography – mass spectrometry analysis of residual lignin changes in softwood kraft pulp during oxygen delignification

The residual lignins from pulps and effluent lignins from oxygen delignification effluents were characterized using pyrolysis – gas chromatography – mass spectrometry in the presence of tetramethylammonium hydroxide. The results indicated that oxidation under alkali oxygen conditions can induce fragmentation in lignin and produce more acid groups, but the lignin maintains most of its C6–C3 units. Oxygen delignification also led to a decrease in diphenyl structures in the residual lignin and an enrichment in concentration of lignin carbohydrate complex structures.Key words: residual lignin, pyrolysis, oxygen delignification.

Total Synthesis of (±)‐Eusiderin G and (±)‐Eusiderin M

Abstract(±)‐Eusiderin G and (±)‐Eusiderin M were first synthesized from pyrogallol, in which the Claisen Rearrangement was used to afford two important C6‐C3 units.

TOTAL SYNTHESIS OF (±)-EUSIDERIN K AND (±)-EUSIDERIN J

(±)-Eusiderin K and (±)-Eusiderin J were first synthesized from pyrogallol, in which the Claisen Rearrangement was used to afford two important C6-C3 units.

Nomenclature of Lignans and Neolignans (IUPAC Recommendations 2000)

Abstract Lignans and neolignans are a large group of natural products characterized by the coupling of two C6C3 units. For nomenclature purposes the C6C3 unit is treated as propylbenzene and numbered from 1 to 6 in the ring, starting from the propyl group, and with the propyl group numbered from 7 to 9, starting from the benzene ring. With the second C6C3 unit the numbers are primed. When the two C6C3 units are linked by a bond between positions 8 and 8' the compound is referred to and named as a lignan. In the absence of the C-8 to C-8' bond, and where the two C6C3 units are linked by a carbon–carbon bond it is referred to and named as a neolignan. The linkage with neolignans may include C-8 or C-8'. Where there are no direct carbon–carbon bonds between the C6C3 units and they are linked by an ether oxygen atom the compound is named as an oxyneolignan. The nomenclature provides for the naming of additional rings and other modifications following standard organic nomenclature procedures for naming natural products. Provision is included to name the higher homologues. The sesquineolignans have three C6C3 units, and dineolignans have four C6C3 units.

A diarylheptanoid intermediate in the biosynthesis of phenylphenalenones in Anigozanthos preissii

The incorporation of 1-phenyl-7-(3,4-dihydroxyphenyl)hepta-1,3-dien-5-one and two molecules of cinnamic acid, respectively, into anigorufone by cultured roots of Anigozanthos preissii provides the first experimental evidence for the biosynthesis of a phenylphenalenone from two C6–C3 units via an open chain type diarylheptanoid.

Donnan Equilibria in Wood-Alkali Interactions. Part I. Quantitative Determination of Carboxyl-, Carboxyl Ester and Phenolic Hydroxyl Groups

Abstract The functional groups in wood that may become ionized by the action of sodium hydroxide consist of carboxyl, phenolic hydroxyl and carbohydrate hydroxyl groups. The extent of ionization is dependent on the pH of the solution and causes the establishment of a Donnan equilibrium between the outer solution phase and that associated with the solid phase. Analytical techniques were developed to determine the carboxyl and phenolic hydroxyl contents of extractive-free mildly saponified hemlock and cottonwood meals using equilibration in the pH range of 12 to 12.5. The determined carboxyl contents, 0.158 and 0.127 meq/g OD wood, respectively, were confirmed by conductometric titrations of wood meal samples methylated with diazomethane prior to saponification with NaOH. Further confirmation was obtained from conductometric titrations of saponified and HCl-washed samples with NaHCO3. The last-mentioned method was also applied to unsaponified hemlock and cottonwood samples to obtain their free carboxyl contents, 0.031 and 0.066 meq/g, respectively. The phenolic hydroxyl contents determined on borohydride-reduced wood samples were 0.260 and 0.147 meq/g, respectively. They were used to estimate the percentages of phenolic units present in in situ lignins. The results obtained suggest that hemlock lignin contains 15.0%, and cottonwood lignin, 14.2% of phenolic C6C3 units.

電極反応を利用した生理活性リグナンおよびネオリグナン類の合成

From a biogenetic point of view, a number of bioactive lignans and neolignans formed by the oxidative dimerization of various C6-C3 units are regio- and stereo-selectively synthesized using electrochemical method, in which anodic oxidation of the corresponding phenols as a key-step is carried out under various conditions. Particularly, a simple method leading to the formation of bicyclo [3. 2. 1] octanones is demonstrated.

ChemInform Abstract: THALLIUM(III) TRIFLUOROACETATE OXIDATION OF SOME ESTERS HAVING TWO C6‐C3 UNITS

Chemischer InformationsdienstVolume 13, Issue 21 Preparative Organic Chemistry ChemInform Abstract: THALLIUM(III) TRIFLUOROACETATE OXIDATION OF SOME ESTERS HAVING TWO C6-C3 UNITS S. NISHIYAMA, Search for more papers by this authorS. YAMAMURA, Search for more papers by this author S. NISHIYAMA, Search for more papers by this authorS. YAMAMURA, Search for more papers by this author First published: May 25, 1982 https://doi.org/10.1002/chin.198221129AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume13, Issue21May 25, 1982 RelatedInformation

Tannins and related compounds. VII. Phenylpropanoid-substituted epicatechnins, cinchonains from Cinchona succirubra. (1).

As a result of an investigation of the relatively lower-molecular-weight phenolics in the bark of Cinchona succirubra (Rubiaceae), cinchonains Ia (1), Ib (2), Ic (3) and Id (4), a new class of flavan-3-ols substituted at the A-ring with a C6-C3 unit, have been isolated, together with caffeic acid (5) and (-)-epicatechin (6). The structures of these compounds have been established on the basis of chemical and spectroscopic evidence. A direct coupling of caffeic acid and (-)-epicatechin leading to the formation of cinchonains has also been achieved.