- Eucommicin A, a β-truxinate lignan from Eucommia ulmoides, is a selective inhibitor of cancer stem cells
-
Cancer stem cells (CSCs) constitute a small population of undifferentiated cells within a tumor that have the ability to self-renew and drive tumor formation, thus behaving as cancer-initiating cancer cells. Therapeutic interventions that eliminate CSCs are necessary to completely cure patients, since CSCs are a crucial source of tumor recurrence and metastasis. An induced CSC-like (iCSCL) model was recently established using induced pluripotent stem cells (iPSCs). In this study, a natural product - eucommicin A - was identified from Eucommia ulmoides leaves by screening for anti-CSC activity using the iCSCL model. Its structure was elucidated by spectroscopic methods as a quinic acid diester of 3,4,3′,4′-tetrahydroxy-β-truxinic acid. Eucommicin A exhibited selective anti-CSC activity and inhibited tumor sphere formation by iCSCL cells. The results of this study suggest that eucommicin A could serve as a lead compound in the development of drugs to abrogate the stemness and self-renewal ability of CSCs.
- Fujiwara, Ayaka,Nishi, Mayuko,Yoshida, Shigeo,Hasegawa, Morifumi,Yasuma, Chieko,Ryo, Akihide,Suzuki, Yoshihito
-
-
Read Online
- SEVEN QUINIC ACID GALLATES FROM QUERCUS STENOPHYLLA
-
A chemical investigation of the bark of Quercus stenophylla has led to the isolation and characterization of all of the possible structural isomers of quinic acid gallates; 3-O-, 4-O-, 5-O-, 3,4-di-O-, 3,5-di-O-, 4,5-di-O- and 3,4,5-tri-O-galloylquinic acids.Evidence for the structures of these compounds was obtained from analysis of the 1H and 13C NMR spectra, and hydrolytic studies.Key Word Index - Quercus stenophylla; Fagaceae; quinic acid gallates; gallotannins; tannase.
- Nishimura, Hiroaki,Nonaka, Gen-Ichiro,Nishioka, Itsuo
-
-
Read Online
- Senecio scandens derivative and application thereof in drugs
-
The invention discloses a senecio scandens derivative and application thereof in drugs. The enecio scandens derivative is the derivative of the effective component chlorogenic acid of senecio scandens. The derivative of the chlorogenic acid is a compound as shown in chemical generation formula I, II, III or IV or one or the combination of the stereisomer, geometrical isomer, tautomer, solvate, polymorphic substance, metabolite, ester, pharmaceutically acceptable salt, prodrug, pharmaceutically acceptable prodrug salt, pharmaceutically acceptable carrier, excipient, diluent, adjuvant and intermedium of the compound. The senecio scandens derivative is used for preparing antiviral drugs. The senecio scandens derivative is good in solubility, high in purity, good in antipyretic performance andespecially suitable for being used as the effective component to prepare antipyretic, anti-inflammation and antibacterial drugs.
- -
-
Paragraph 0019; 0032; 0037
(2018/08/04)
-
- Analysis of protein-phenolic compound modifications using electrochemistry coupled to mass spectrometry
-
In the last decade, electrochemical oxidation coupled with mass spectrometry has been successfully used for the analysis of metabolic studies. The application focused in this study was to investigate the redox potential of different phenolic compounds such as the very prominent chlorogenic acid. Further, EC/ESI-MS was used as preparation technique for analyzing adduct formation between electrochemically oxidized phenolic compounds and food proteins, e.g., alpha-lactalbumin or peptides derived from a tryptic digestion. In the first step of this approach, two reactant solutions are combined and mixed: one contains the solution of the digested protein, and the other contains the phenolic compound of interest, which was, prior to the mixing process, electrochemically transformed to several oxidation products using a boron-doped diamond working electrode. As a result, a Michael-type addition led to covalent binding of the activated phenolic compounds to reactive protein/peptide side chains. In a follow-up approach, the reaction mix was further separated chromatographically and finally detected using ESI-HRMS. Compound-specific, electrochemical oxidation of phenolic acids was performed successfully, and various oxidation and reaction products with proteins/peptides were observed. Further optimization of the reaction (conditions) is required, as well as structural elucidation concerning the final adducts, which can be phenolic compound oligomers, but even more interestingly, quite complex mixtures of proteins and oxidation products.
- Kallinich, Constanze,Schefer, Simone,Rohn, Sascha
-
-
- Synthesis, Structure, and Tandem Mass Spectrometric Characterization of the Diastereomers of Quinic Acid
-
(-)-Quinic acid possess eight possible stereoisomers, which occur both naturally and as products of thermal food processing. In this contribution, we have selectively synthesized four isomers, namely, epi-quinic acid, muco-quinic acid, cis-quinic acid, and scyllo-quinic acid, to develop a tandem LC-MS method identifying all stereoisomeric quinic acids. Four derivatives have been unambiguously characterized by single-crystal X-ray crystallography. The missing diastereomers of quinic acid were obtained by nonselective isomerization of (-)-quinic acid using acetic acid/concentrated H2SO4 allowing chromatographic separation and assignment of all diastereomers of quinic acid. We report for the first time that a full set of stereoisomers are reliably distinguishable on the basis of their tandem mass spectrometric fragment spectra as well as their elution order. A rationale for characteristic fragmentation mechanisms is proposed. In this study, we also observed that muco-quinic acid, scyllo-quinic acid, and epi-quinic acid are present in hydrolyzed Guatemalan roasted coffee sample as possible products of roasting.
- Deshpande, Sagar,Matei, Marius Febi,Jaiswal, Rakesh,Bassil, Bassem S.,Kortz, Ulrich,Kuhnert, Nikolai
-
p. 7298 - 7306
(2016/10/07)
-
- A novel stereoselective synthesis of (-)-quinic acid starting from the naturally abundant (-)-shikimic acid
-
A new stereoselective synthesis of (-)-quinic acid from the naturally abundant (-)-shikimic acid is described. Ethyl shikimate 2 was first prepared in 97% yield via esterification of (-)-shikimic acid according to a previous report. Ester 2 was then transformed into an epimeric mixture of 3,4-O-benzylidene shikimate 3, which was directly converted into compound 4 in 90% yield (over 2 steps from ester 2) via an NBS-mediated acetal ring-opening reaction. Acetylization of the hydroxyl group at the C-5 position of compound 4 gave compound 5 in 98% yield. Compound 5 was transformed into compound 6 in 91% yield via a highly stereoselective Ru-catalyzed dihydroxylation. Subsequently, compound 6 was converted into epoxide 7 in 82% yield via an intramolecular SN2 type substitution. A regioselective epoxide-opening of compound 7 by PPh3-I2 complex furnished an iodo compound 8 in 79% yield. Removal of the iodine atom in compound 8 by Pd/C-catalyzed hydrogenation produced compound 9 in 92% yield. Methanolysis of compound 9 gave methyl quinate 10 in 92% yield. Finally, hydrolysis of compound 10 afforded the targeted compound (-)-quinic acid 1 in 90% yield. The title compound (-)-quinic acid 1 was stereoselectively synthesized through 10 steps starting from (-)-shikimic acid in 38% overall yield.
- Zhang, Wei,Zhu, Xing-Liang,Ding, Wei,Shi, Xiao-Xin
-
p. 1375 - 1381
(2015/11/25)
-
- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
-
We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
- Senthilkumar,Asha
-
supporting information
p. 8931 - 8934
(2015/05/27)
-
- 1,5-DI-O-Isoferuloylquinic acid and other phenolic compounds from pollen of calendula officinalis
-
A new phenylpropanoid that was identified as 1,5-di-O-isoferuloylquinic acid (1) and 17 known compounds including 1,5-di-O-feruloylquinic acid (2), which was obtained for the first time from a plant and was synthesized previously, were isolated from pollen of Calendula officinalis. Compounds 1 and 2 were the dominant phenolic compounds from pollen of C. officinalis. It was found that 1 possessed pronounced inhibitory activity against tyrosinase (IC50 11.26μg/mL).
- Olennikov,Kashchenko
-
p. 589 - 593
(2015/02/02)
-
- Prenylated coumarins: Natural phosphodiesterase-4 inhibitors from toddalia asiatica
-
Bioassay-guided fractionation of the ethanolic extract of the roots of Toddalia asiatica led to the isolation of seven new prenylated coumarins (1-7) and 14 known analogues (8-21). The structures of 1-7 were elucidated by spectroscopic analysis, and their absolute configurations were determined by combined chemical methods and chiral separation analysis. Compounds 1-5, named toddalin A, 3t′-O-demethyltoddalin A, and toddalins B-D, represent an unusual group of phenylpropenoic acid-coupled prenylated coumarins. Compounds 1-21 and four modified analogues, 10a, 11a, 13a, and 17a, were screened by using tritium-labeled adenosine 3,5-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 3, 8, 10, 10a, 11, 11a, 12, 13, 17, and 21 exhibited inhibition with IC50 values less than 10 μM. Toddacoumalone (8), the most active compound (IC50 = 0.14 μM), was more active than the positive control, rolipram (IC50 = 0.59 μM). In addition, the structure-activity relationship and possible inhibitory mechanism of the active compounds are also discussed.
- Lin, Ting-Ting,Huang, Yi-You,Tang, Gui-Hua,Cheng, Zhong-Bin,Liu, Xin,Luo, Hai-Bin,Yin, Sheng
-
p. 955 - 962
(2014/05/20)
-
- Quinic acid derivatives from Pimpinella brachycarpa exert anti-neuroinflammatory activity in lipopolysaccharide-induced microglia
-
Five new quinic acid derivatives (1-5), together with 10 known quinic acid derivatives (6-15), were isolated from the MeOH extract of Pimpinella brachycarpa (Umbelliferae). Their structures were established on the basis of spectroscopic analyses including extensive 2D NMR studies (COSY, HMQC and HMBC). Isolated compounds 1-15 were evaluated for their inhibitory activities on nitric oxide (NO) production in an activated murine microglial cell line. Compounds 2, 3, 8 and 11 significantly inhibited NO production without high cell toxicity in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cell line (IC50 = 4.66, 12.52, 9.04 and 12.11 μM, respectively).
- Lee, Seung Young,Moon, Eunjung,Kim, Sun Yeou,Lee, Kang Ro
-
supporting information
p. 2140 - 2144
(2013/05/09)
-
- Acylated sucroses and acylated quinic acids analogs from the flower buds of Prunus mume and their inhibitory effect on melanogenesis
-
The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang Province, China, showed an inhibitory effect on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. From the methanolic extract, five acylated sucroses, mumeoses A-E, and three acylated quinic acid analogs, 5- O-(E)-p-coumaroylquinic acid ethyl ester, and mumeic acid-A and its methyl ester, were isolated together with 13 known compounds. The chemical structures of the compounds were elucidated on the basis of chemical and physicochemical evidence. Inhibitory effects of the isolated compounds on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were also investigated. Acylated quinic acid analogs substantially inhibited melanogenesis. In particular, 5-O-(E)-feruloylquinic acid methyl ester exhibited a potent inhibitory effect [inhibition (%): 21.5 ± 1.0 (P 97% at 10 μM]. It is concluded that acylated quinic acid analogs are promising therapeutic agents for the treatment of skin disorders.
- Nakamura, Seikou,Fujimoto, Katsuyoshi,Matsumoto, Takahiro,Nakashima, Souichi,Ohta, Tomoe,Ogawa, Keiko,Matsuda, Hisashi,Yoshikawa, Masayuki
-
p. 128 - 136
(2013/10/21)
-
- Synthesis of 3-cyclohexylpropyl caffeate from 5-caffeoylquinic acid with consecutive enzymatic conversions in ionic liquid
-
We developed a convenient one-pot procedure for conversion of 5-caffeoylquinic acid to 3-cyclohexylpropyl caffeate, which exhibits an antiproliferative effect toward various human tumor cells. The procedure was comprised of two consecutive reactions by chlorogenate hydrolase (EC 3.1.1.42) from Aspergillus japonicus and Candida antarctica lipase B, and was performed using an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide, as the reaction solvent. When various caffeoylquinic acids from coffee beans, namely, 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were used, the first alcoholysis reaction with methanol using chlorogenate hydrolase produced methyl caffeate with conversion yields of 60.0%, 61.3%, 86.0%, 92.7%, and 114.0%, respectively, to each individual substrate. Two caffeoyl groups of dicaffeoylquinic acids would be used for the synthesis of methyl caffeate. In the subsequent transesterification reaction by C. antarctica lipase B with 3-cyclohexyl-1-propanol, the methyl caffeate produced was converted to 3-cyclohexylpropyl caffeate under reduced pressure to remove the by-product methanol. In the one-pot synthesis, the methyl caffeate was transesterified efficiently to 3-cyclohexylpropyl caffeate by C. antarctica lipase B with deactivation of chlorogenate hydrolase by taking advantage of the difference between the optimum temperatures for the two enzymes. This system provided 12.8 mM 3-cyclohexylpropyl caffeate from 15 mM 5-caffeoylquinic acid with conversion yield of 85.3%.
- Kurata, Atsushi,Takemoto, Shintaro,Fujita, Tokio,Iwai, Kazuya,Furusawa, Mina,Kishimoto, Noriaki
-
experimental part
p. 161 - 167
(2012/01/30)
-
- Thermal stability of 5-o-caffeoylquinic acid in aqueous solutions at different heating conditions
-
Chlorogenic acid is a naturally occurring phenolic compound found in all higher plants. This component, being the ester of caffeic acid with quinic acid, is an important biosynthetic intermediate and plays an important role in the plant's response to stress. Potential uses of chlorogenic acid are suggested in pharmaceuticals, foodstuffs, feed additives, and cosmetics due to its recently discovered biomedical activity. This finding caused new interest in chlorogenic acid properties, its isomers, and its natural occurrence. It has been found that as many as nine compounds (chlorogenic acid derivatives and its reaction product with water) can be formed from 5-o-caffeoylquinic acid during the heating of its water solution. Three of them, two hydroxylated 5-o-caffeoylquinic acid derivatives and 4,5-dicaffeoylquinic acid, have been not reported, yet. The amount of each formed component depends on the heating time and temperature. The presented results are important for researchers investigating plant metabolism and looking for new plant components. The transformation product can be mistakenly treated as a new component, not found before in the examined plant, or can be a cause of erroneous quantitative estimations of plant composition.
- Dawidowicz, Andrzej L.,Typek, Rafal
-
experimental part
p. 12578 - 12584
(2011/10/30)
-
- The anti-thrombotic active constituents from Centella asiatica
-
The in vitro effects of a methanol extract from the aerial parts of Centella asiatica on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. 3,5-Di-O-caffeoyl quinic acid, 1,5-di-O-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, and chlorogenic acid, together with asiaticoside, kaempferol, quercetine, kaempferol-3-O-β-D-glucoside and quercetin-3-O-β-D-glucoside were all isolated from the methanol extract. Amongst these, only 3,5-di-O-caffeoylquinic acid showed significant inhibition of shear-induced platelet activation and dynamic coagulation. The reactive curve of the inhibitory effect on the platelet reaction and the dynamic coagulation showed a bell-shape.
- Satake, Toshiko,Kamiya, Kohei,An, Yin,Oishi, Tomomi,Yamamoto, Junichiro
-
p. 935 - 940
(2008/01/27)
-
- Hydroaromatic equilibration during biosynthesis of shikimic acid
-
The expense and limited availability of shikimic acid isolated from plants has impeded utilization of this hydroaromatic as a synthetic starting material. Although recombinant Escherichia coli catalysts have been constructed that synthesize shikimic acid from glucose, the yield, titer, and purity of shikimic acid are reduced by the sizable concentrations of quinic acid and 3-dehydroshikimic acid that are formed as byproducts. The 28.0 g/L of shikimic acid synthesized in 14% yield by E. coli SP1.1/pKD12.138 in 48 h as a 1.6:1.0:0.65 (mol/mol/mol) shikimate/quinate/dehydroshikimate mixture is typical of synthesized product mixtures. Quinic acid formation results from the reduction of 3-dehydroquinic acid catalyzed by aroE-encoded shikimate dehydrogenase. Is quinic acid derived from reduction of 3-dehydroquinic acid prior to synthesis of shikimic acid? Alternatively, does quinic acid result from a microbe-catalyzed equilibration involving transport of initially synthesized shikimic acid back into the cytoplasm and operation of the common pathway of aromatic amino acid biosynthesis in the reverse of its normal biosynthetic direction? E. coli SP1.1/pSC5.214A, a construct incapable of de novo synthesis of shikimic acid, catalyzed the conversion of shikimic acid added to its culture medium into a 1.1:1.0:0.70 molar ratio of shikimate/quinate/dehydroshikimate within 36 h. Further mechanistic insights were afforded by elaborating the relationship between transport of shikimic acid and formation of quinic acid. These experiments indicate that formation of quinic acid during biosynthesis of shikimic acid results from a microbe-catalyzed equilibration of initially synthesized shikimic acid. By apparently repressing shikimate transport, the aforementioned E. coli SP1.1/pKD12.138 synthesized 52 g/L of shikimic acid in 18% yield from glucose as a 14:1.0:3.0 shikimate/quinate/dehydroshikimate mixture.
- Knop,Draths,Chandran,Barker,Von Daeniken,Weber,Frost
-
p. 10173 - 10182
(2007/10/03)
-
- Benzene-free synthesis of phenol
-
Heating shikimic acid in near-critical water leads to the formation of phenol. Since shikimic acid can now be obtained by the microbial conversion of glucose, a benzene-freer route to phenol could become an alternative to the industrial Hock oxidation of cumene derived from benzene (see scheme).
- Gibson, James M.,Thomas, Phillip S.,Thomas, Joshua D.,Barker, Jessica L.,Chandran, Sunil S.,Harrup, Mason K.,Draths, Karen M.,Frost, John W.
-
p. 1945 - 1948
(2007/10/03)
-
- Benzene-free synthesis of hydroquinone
-
All current routes for the synthesis of hydroquinone utilize benzene as the starting material. An alternate route to hydroquinone has now been elaborated from glucose. While benzene is a volatile carcinogen derived from nonrenewable fossil fuel feedstocks, glucose is nonvolatile, nontoxic, and derived from renewable plant polysacharrides. Glucose is first converted into quinic acid using microbial catalysis. Quinic acid is then chemically converted into hydroquinone. Under fermentor-controlled conditions, Escherichia coli QP1.1/pKD12.138 synthesizes 49 g/L of quinic acid from glucose in 20% (mol/mol) yield. Oxidative decarboxylation of quinic acid in clarified, decolorized, ammonium ion-free fermentation broth with NaOCl and subsequent dehydration of the intermediate 3(R),5(R)-trihydroxycyclohexanone afforded purified hydroquinone in 87% yield. Halide-free, oxidative decarboxylation of quinic acid in fermentation broth with stoichiometric quantities of (NH4)2Ce(SO4)3 and V2O5 afforded hydroquinone in 91% and 85% yield, respectively. Conditions suitable for oxidative decarboxylation of quinic acid with catalytic amounts of metal oxidant were also identified. Ag3PO4 at 2 mol % relative to quinic acid in fermentation broth catalyzed the formation of hydroquinone in 74% yield with K2S2O8 serving as the cooxidant. Beyond establishing a fundamentally new route to an important chemical building block, oxidation of microbe-synthesized quinic acid provides an example of how the toxicity of aromatics toward microbes can be circumvented by interfacing chemical catalysis with biocatalysis.
- Ran,Knop,Draths,Frost
-
p. 10927 - 10934
(2007/10/03)
-
- A concise enantio- and diastereo-controlled synthesis of (-)-quinic acid and (-)-shikimic acid
-
(-)-Quinic acid and (-)-shikimic acid, both recognized as the key intermediates in the shikimate pathway in plants and microorganisms, have been synthesized concisely in an enantio- and diastereo-controlled manner starting from a synthetic equivalent of (R)-4-hydroxycyclohex-2-enone.
- Hiroya, Kou,Ogasawara, Kunio
-
p. 2033 - 2034
(2007/10/03)
-
- MALONATED FLAVONOL GLYCOSIDES AND 3,5-DICAFFEOYLQUINIC ACID FROM PEARS
-
Key Word Index--Pyrus communis; Rosaceae; pears; malonated flavonol glucosides; 3,5-dicaffeoylquinic acid.Abstract--3-O-(6''-O-malonyl)-β-Glucosides of quercetin, kaempferol, isorhamnetin and 3,5-dicaffeoylquinic acid were isolated and identified from leaves of pears.The compounds are also present in the fruits.
- Wald, Burkard,Wray, Victor,Galensa, Rudolf,Herrmann, Karl
-
p. 663 - 664
(2007/10/02)
-
- Constituents of Pollen. XV. Constituents of Biota orientalis (L.) ENDL. (1)
-
Two new compounds have been isolated from the pollen grains of Biota orientalis (L.) ENDL., and these compounds were determined to be 16-feruloyloxypalmitic acid (I) and 5-O-p-coumaroylquinic acid methyl ester (II) by chemical and spectroscopic methods. p-Coumaric acid, ferulic acid, quercitin, epi-ikshusterol, luteolin, populnin and β-sitosteryl β-D-glucoside were also isolated.Keywords-Biota orientalis; Cupressaceae; pollen grains; 16-feruloyloxypalmitic acid; 5-O-p-coumaroylquinic acid methyl ester.
- Ohmoto, Taichi,Yamaguchi, Kyoko
-
p. 807 - 809
(2007/10/02)
-
- FLAVONOID CONSTITUENTS OF EPHEDRA ALATA
-
Two new flavonol glucosides have been identified in Ephedra alata, namely, herbacetin 8-methyl ether 3-O-glucoside-7-O-rutinoside and herbacetin 7-O-(6''-quinylglucoside).The known flavonoids vicenin II, lucenin III, kaempferol 3-rhamnoside, quercetin 3-rhamnoside and herbacetin 7-glucoside were also found.The structure of the isolated compounds was determined mostly by FABMS and 1H NMR spectroscopy.The final structure of the new compounds and of herbacetin 7-glucoside was confirmed by 13C NMR soectroscopy. Key Word Index - Ephedra alata; Ephedraceae; herbacetin 8-methyl ether 3-O-glucoside-7-O-rutinoside; herbacetin 7-O-(6''-quinyl glucoside); flavonol O-glycosides and C-glycosylflavones.
- Nawwar, Mahmoud A. M.,El-Sissi, Hassan I.,Barakat, Heba H.
-
p. 2937 - 2940
(2007/10/02)
-
