- 11-β-hydroxysterols as possible endogenous stimulators of mitochondrial biogenesis as inferred from epicatechin molecular mimicry
-
Currently, there is great interest in identifying endogenous (i.e. physiological) stimulators of mitochondrial biogenesis (MB), in particular, those that may mediate the effects of exercise. The molecular size of the cacao flavanols (epicatechin and catechin) highly resembles that of sterols and epicatechin has been reported to activate cells surface receptors leading to the stimulation of MB in endothelial and skeletal muscle cells translating into enhanced exercise capacity. We therefore hypothesize, that epicatechin may be acting as a structural mimic of an as yet unknown sterol capable of stimulating MB. We developed a new synthetic process for obtaining enantiomerically pure preparations of (-)-epicatechin and (+)-epicatechin. Applying spatial analytics and molecular modeling, we found that the two isoforms of epicatechin, (-) and (+), have a structural resemblance to 11-β-hydroxypregnenolone, a sterol with no previously described biological activity. As reported in this proof-of-concept study performed in primary cultures of endothelial and muscle cells, 11-β-hydroxypregnenolone is one of the most potent inducers of MB as significant activity can be detected at femtomolar levels. The relative potency of (-)/(+)-epicatechin isoforms and on inducing MB correlates with their degree of spatial homology towards the 11-β-hydroxypregnenolone. On the basis of these results, the detailed in vivo characterization of the potential for these sterols to act as endogenous modulators of MB is warranted.
- Dugar, Sundeep,Villarreal, Francisco,Hollinger, Frank H.,Mahajan, Dinesh,Ramirez-Sanchez, Israel,Moreno-Ulloa, Aldo,Ceballos, Guillermo,Schreiner, George
-
-
- Effects of epigallocatechin gallate on the stability of epicatechin in a photolytic process
-
Catechins belonging to polyhydroxylated polyphenols are the primary compounds found in green tea. They are associated with many physiological properties. Epicatechin (EC) is a non-gallate-type catechin with four phenolic hydroxyl groups attached. The changes in EC treated with color light illumination in an alkaline condition were investigated by chromatographic and mass analyses in this study. In particular, the superoxide anion radical (O2??) was investigated during the EC photolytic process. EC is unstable under blue light illumination in an alkaline solution. When EC was treated with blue light illumination in an alkaline solution, O2?? was found to occur via a photosensitive redox reaction. In addition, the generation of monomeric, dimeric, and trimeric compounds is investigated. On the other hand, epigallocatechin gallate (EGCG), which is a gallate-type catechin, is stable under blue light illumination in an alkaline solution. Adding EGCG, during the blue light illumination treatment of EC decreased photolytic formation, suggesting that gallate-type catechins can suppress the photosensitive oxidation of EC. Gallate-type catechins are formed via the esterification of non-gallate-type catechins and gallic acid (GA). The carbonyl group on the gallate moiety of gallate-type catechins appears to exhibit its effect on the stability against the photosensitive oxidation caused by blue light illumination.
- Huang, Shiuh-Tsuen,Hung, Yi-An,Yang, Meei-Ju,Chen, Iou-Zen,Yuann, Jeu-Ming P.,Liang, Ji-Yuan
-
-
- Metabolic characterization of the anthocyanidin reductase pathway involved in the biosynthesis of flavan-3-ols in elite Shuchazao tea (Camellia sinensis) cultivar in the field
-
Anthocyanidin reductase (ANR) is a key enzyme in the ANR biosynthetic pathway of flavan-3-ols and proanthocyanidins (PAs) in plants. Herein, we report characterization of the ANR pathway of flavan-3-ols in Shuchazao tea (Camellia sinesis), which is an elite and widely grown cultivar in China and is rich in flavan-3-ols providing with high nutritional value to human health. In our study, metabolic profiling was preformed to identify two conjugates and four aglycones of flavan-3-ols: (-)-epigallocatechin-gallate [(-)-EGCG], (-)-epicatechin-gallate [(-)-ECG], (-)-epigallocatechin [(-)-EGC], (-)-epicatechin [(-)-EC], (+)-catechin [(+)-Ca], and (+)-gallocatechin [(+)-GC], of which (-)-EGCG, (-)-ECG, (-)-EGC, and (-)-EC accounted for 70-85% of total flavan-3-ols in different tissues. Crude ANR enzyme was extracted from young leaves. Enzymatic assays showed that crude ANR extracts catalyzed cyanidin and delphinidin to (-)-EC and (-)-Ca and (-)-EGC and (-)-GC, respectively, in which (-)-EC and (-)-EGC were major products. Moreover, two ANR cDNAs were cloned from leaves, namely CssANRa and CssANRb. His-Tag fused recombinant CssANRa and CssANRb converted cyanidin and delphinidin to (-)-EC and (-)-Ca and (-)-EGC and (-)-GC, respectively. In addition, (+)-EC was observed from the catalysis of recombinant CssANRa and CssANRb. Further overexpression of the two genes in tobacco led to the formation of PAs in flowers and the reduction of anthocyanins. Taken together, these data indicate that the majority of leaf flavan-3-ols in Shuchazao's leaves were produced from the ANR pathway.
- Zhao, Lei,Jiang, Xiao-Lan,Qian, Yu-Mei,Wang, Pei-Qiang,Xie, De-Yu,Gao, Li-Ping,Xia, Tao
-
-
- A catechin preparation method of compound (by machine translation)
-
The invention relates to a method for preparing a catechin compound. The method comprises the following steps: by taking 2,4,6-trihydroxy acetophenone and p-hydroxy benzaldehyde as raw materials, carrying out condensation reaction, restored deoxidation, cyclization reaction of acid catalysis, so as to obtain the catechin compound. The invention also provides a technology for producing the catechin compound. In the synthesis process of an immediate 9, reduction is carried out by using sodium borohydride which is catalyzed by a lewis acid, so that side reaction caused by double bond transfer is greatly reduced while a highly toxic reagent osmium tetroxide is replaced with hydrogen peroxide oxidation.
- -
-
-
- NOVEL APPROACH FOR SYNTHESIS OF CATECHINS
-
A process for synthesis of enatiomerically pure or enatiomerically enriched or racemic mixture of (+and/or?) epicatechin echm and its intermediates, comprising the steps of: (i) obtaining penta-protected quercetin; (ii) reducing the penta-protected quercetin obtained from step (i); (iii) optionally deprotecting the compound of step (ii); (iv) reducing the compound obtained from step (ii) or step (iii) in the presence of a chiral/achiral reducing agent to obtain a chiral intermediate; (v) deprotecting and/or hydrogenation of the chiral intermediate obtained from step (iv) to obtain (?)-epicatechin; (vi) optionally simultaneously deprotecting and by drogenation of the compound obtained from step (ii) to obtain racemic epicatechin.
- -
-
-
- NOVEL PROCESS FOR SYNTHESIS OF POLYPHENOLS
-
The present invention provides synthetic processes for preparing racemic and/or optically pure epicatechin, epigallocatechin and related polyphenols as such or as their variously functionalized derivatives. A principle objective of the disclosure is to provide a new and useful method of synthesis to obtain polyphenols in isomerically pure and/or racemic forms.
- -
-
Paragraph 0150; 0151; 0152; 0153
(2014/02/16)
-
- A NOVEL PROCESS FOR SYNTHESIS OF POLYPHENOLS
-
The present invention provides synthetic processes for preparing racemic and/or optically pure epicatechin, epigallocatechin and related polyphenols as such or as their variously functionalized derivatives.
- -
-
Page/Page column 31
(2012/08/08)
-
- Photochemistry synthesis. Part 2: Enantiomerically pure polyhydroxy-1,1,3-triarylpropan-2-ols
-
A new method to open the heterocyclic ring of flavan-3-ols via photolytic cleavage of the ether bond, with stereoselective trapping of the intermediates with phloroglucinol to obtain phloroglucinol grafted derivatives of flavan-3-ols, was developed. Photolysis of catechin and epicatechin, respectively, in the presence of phloroglucinol yielded the enantiomeric (1S,2S)- and (1R,2R)-1,3-di(2,4,6-trihydroxyphenyl)-1-(3,4-dihydroxyphenyl) propan-2-ols, respectively. The absolute configuration at C-1 and C-2 was determined by electronic circular dichroism (experimental and calculated) and these results confirmed that the trapping mechanism is controlled by the C-3 configuration of the flavan-3-ol.
- Wilhelm-Mouton, Anke,Bonnet, Susan L.,Ding, Yuanqing,Li, Xing-Cong,Ferreira, Daneel,Van Der Westhuizen, Jan H.
-
experimental part
p. 18 - 24
(2012/03/26)
-
- High molecular weight persimmon (Diospyros kaki L.) proanthocyanidin: A highly galloylated, a-linked tannin with an unusual flavonol terminal unit, myricetin
-
MALDI-TOF MS suggested that the high molecular weight proanthocyanidin (condensed tannin) from persimmon (Diospyros kaki L.) pulp comprised a heteropolyflavanol series with flavan-3-O-galloylated extenders, flavan-3-ol and flavonol terminal units, and A-type interflavan linkages. Thiolysis-HPLC-ESI-MS with DAD, electrochemical, and ESI-MS detection confirmed a previously unreported terminal unit, the flavonol myricetin, in addition to the typical flavan-3-ols catechin and epigallocatechin gallate. The extender units were epicatechin, epigallocatechin, (epi)gallocatechin-3-O-gallate, and (epi)catechin-3-O-gallate. The crude tannin had a high prodelphinidin content (65%) and a high degree of 3-O-galloylation (72%). The material was fractionated on Toyopearl TSK-HW-50-F to yield fractions distinguished by degree of polymerization (DP). Thiolysis suggested that the persimmon tannin was composed of polymers ranging from 7 to 20 kDa (DP 19-47), but sizes estimated by GPC were 50-70% smaller. The crude material was chemically degraded with acid to yield products that were amenable to NMR and ESI-MS analysis, which were used to establish for the first time that persimmon tannin has a mixture of B-type and A-type linkages. 2010 American Chemical Society.
- Li, Chunmei,Leverence, Rachael,Trombley, John D.,Xu, Shufen,Yang, Jie,Tian, Yan,Reed, Jess D.,Hagerman, Ann E.
-
experimental part
p. 9033 - 9042
(2011/05/05)
-
- Epimerization of tea catechins under weakly acidic and alkaline conditions
-
Tea catechins in a buffer at pH 7 with N2 replacing O 2 epimerized rapidly at 80 °C with less than 10% of oxidative side reactions and gave catechin epimers in a 50-63% yield. The epimerization of catechins with three hydroxyl groups was faster than with two groups, and of galloyl-free catechins was faster than catechins with a galloyl ester.
- Ishino, Nobuyoshi,Yanase, Emiko,Nakatsuka, Shin-Ichi
-
scheme or table
p. 875 - 877
(2011/07/30)
-
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
-
Anthocyanidin reductase (ANR) from Vitis vinifera catalyzes an NADPH-dependent double reduction of anthocyanidins producing a mixture of (2S,3R)- and (2S,3S)-flavan-3-ols. At pH 7.5 and 30°C, the first hydride transfer to anthocyanidin is irreversible, and no intermediate is released during catalysis. ANR reverse activity was assessed in the presence of excess NADPq. Analysis of products by reverse phase and chiral phase HPLC demonstrates that ANR acts as a flavan-3-ol C3-epimerase under such conditions, but this is only observed with 2R-flavan-3-ols, not with 2S-flavan-3-ols produced by the enzyme in the forward reaction. In the presence of deuterated coenzyme 4S-NADPD, ANR transforms anthocyanidins into dideuterated flavan-3-ols. The regiospecificity of deuterium incorporation into catechin and afzelechin - derived from cyanidin and pelargonidin, respectively - was analyzed by liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS), and it was found that deuterium was always incorporated at C2 and C4. We conclude that 3-epimerization should be achieved by tautomerization between the two hydride transfers and that this produces a quinone methide intermediate which serves as C4 target of the second hydride transfer, thereby avoiding any stereospecific modification of carbon 3. The inversion of C2 stereochemistry required for reverse epimerization suggests that the 2S configuration induces an irreversible product dissociation.
- Gargouri, Mahmoud,Chaudiere, Jean,Manigand, Claude,Mauge, Chloe,Bathany, Katell,Schmitter, Jean-Marie,Gallois, Bernard
-
experimental part
p. 219 - 227
(2011/11/05)
-
- Proanthocyanidins and a phloroglucinol derivative from Rumex acetosa L.
-
From the ethyl acetate soluble fraction of an acetone-water extract of the aerial parts of Rumex acetosa L. (Polygonaceae), a variety of monomeric flavan-3-ols (catechin, epicatechin, epicatechin-3-O-gallate), A- and B-type procyanidins and propelargonidins (15 dimers, 7 trimers, 2 tetramers) were isolated with 5 so far unknown natural products. Dimers: procyanidin B1, B2, B3, B4, B5, B7, A2, epiafzelechin-(4β→8)-epicatechin, epiafzelechin-(4β→8)-epicatechin-3-O-gallate (new natural product), epiafzelechin-(4β→6)-epicatechin-3-O-gallate (new natural product), epiafzelechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate, B2-3′-O-gallate, B2-3,3′-di-O-gallate, B5-3′-O-gallate, and B5-3,3′-di-O-gallate. Trimers: procyanidin C1, epiafzelechin-(4β→8)-epicatechin-(4β→8)-epicatechin (new natural product), epicatechin-(4β→8)-epicatechin-(4β→8)-catechin, cinnamtannin B1, cinnamtannin B1-3-O-gallate (new natural product), tentatively epicatechin-(2β→7, 4β→8)-epiafzelechin-(4α→8)-epicatechin (new natural product), and epicatechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate. Tetramers: procyanidin D1 and parameritannin A1. All compounds were elucidated by ESI-MS, CD spectra, 1D- and 2D-NMR experiments as free phenols or peracetylated derivatives and, in part, after partial acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin polymer was also isolated, purified and its chemical composition studied by 13C NMR. In addition a so far unknown phloroglucinolglycoside (1-O-β-d-(2,4-dihydroxy-6-methoxyphenyl)-6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-glucopyranoside) was isolated.
- Bicker,Petereit,Hensel
-
experimental part
p. 483 - 495
(2010/06/15)
-
- PREPARATION OF (+)-CATECHIN, (-)-EPICATECHIN, (-)-CATECHIN, (+)-EPICATECHIN, AND THEIR 5,7,3',4'-TETRA-O-BENZYL ANALOGUES
-
Processes for preparing racemic mixtures of 5,7,3',4'-tetra-O-benzyl-(±)-catechin and (±)-epicatechin involves (i) condensing 2-hydroxy-4,6-bis(benzyloxy)-acetophenone and 3,4-bis(benzyloxy)benzaldehyde, cyclizing the resulting compound, oxidizing the resulting compound; (ii) dihydroxylating (E)-3-(3',4'-bis(benzyloxy)phenyl)prop-2-ene-1 -ol and reducing the 1 ,2-diol; or (iii) coupling 3,5-bis(benzyloxy)phenol with (£)-3,5-bis(benzyloxy)-2-(3',4'-bis(benzyloxy)phenyl)allyl)phenol and cyclizing the resulting chalcone. A process for preparing the benzylated epimers of catechin and epicatechin involves seven steps. 3,4-Bis(benzyloxy)benzaldehyde is coupled with 2-hydroxy-4,6-benzyloxy-acetophenone to form a chalcone. The chalcone is selectively reduced to an alkene. The phenolic group of the alkene is protected. The protected alkene is asymetrically dihydroxylated. The resulting compound is deprotected, cyclized, and finally hydrolyzed. Epimers resulting from these processes are chemically resolved or separated by chiral high pressure liquid chromatography. Also disclosed is a method for preparing enantiomerically pure 5,7,3',4'-tetra-O-benzyl-(+)-catechin from a racemic mixture using dibenzoyl-L-tartaric acid monomethyl ester. Further, disclosed is an improved process for preparing dibenzoyl-L-tartaric acid monomethyl ester.
- -
-
Page/Page column 13; 36-37
(2010/11/25)
-
- IODINATION AND DEUTERATION OF CATECHIN DERIVATIVES
-
The preparation and 1H and 13C nuclear magnetic reonance spectra of ten monoiodocatechin derivatives are described.The iodination of catechin with N-iodosuccinimide (NIS) takes place regiospecifically at C-6 in acetone but preferentially at C-8 in dimethylformamide; both products can be derivatized at oxygen in alkali medium but lose iodine in the presence of acid. 3',4',5,7,-Tetra-O-methylcatechin reacts with NIS regiospecifically at C-8 while catechin pentaacetate resists iodination.The debromination of 6-bromo- and 6,8-dibromocatechin with sodium sulfite in CD3CN/D2O is accompained by H/D-exchange at C-6 and C-8.The synthesis of catechin pentaacetate from partially deuterated catechin and its conversion to terta-O-methylcatechin proceed without H/D-exchange and permit distinction between the H-6 and H-8 chemical shifts.
- Kiehlmann, E.,Lehto, N.,Cherniwchan, D.
-
p. 2431 - 2439
(2007/10/02)
-
- Tannins and Related Compounds. LIX. Aesculitannins, Novel Proanthocyanidins with Doubly-Bonded Structures from Aesculus hippocastanum L.
-
A chemical examination of the seed shells of Aesculus hyppocastanum L.has led to the isolation of proanthocyanidins A-6 (10) and A-7 (11), and aesculitannins A (12), B (13), C (14), D (15), E (16), F (17) and G (18).On the basis of chemical and spectroscopic evidence, proanthocyanidins A-6 (10) and A-7 (11) have been determined to be A-type dimers each possessing a C-4, C-6 interflavanoid linkage, while aesculitannins A (12), B (13), C (14), D (15), E (16), F (17) and G (18) have been characterized as oligomeric proanthocyanidins possessing A-type unit(s) in each molecule.In addition, the presence of (-)-epicatechin (1), proanthocyanidins B-5 (3), A-2 (4), A-4 (5) and C-1 (6), epicatechin-(4β->6)-epicatechin-(4β->6)-epicatechin (7), and cinnamtannins B1 (8) and B2 (9) was also demonstrated Keywords---Aesculus hippocastanum; Hippocastanaceae; aesculitannin; doubly-bonded proanthocyanidin; procyanidin; condensed tannin; flavan-3-ol; thiolytic degradation; epimerization; hydrogen peroxide oxidation
- Morimoto, Satoshi,Nonaka, Gen-ichiro,Nishioka, Itsuo
-
p. 4717 - 4729
(2007/10/02)
-
- DEOXYGENATION OF ALDEHYDES AND KETONES WITH SODIUM CYANOBOROHYDRIDE
-
Treatment of hydroxy-substituted aromatic aldehydes and ketones with sodium cyanoborohydride yields the corresponding methylene compounds under conditions which favor intermediate carbonium ion formation.
- Elliger, Carl A.
-
p. 1315 - 1324
(2007/10/02)
-
- Physico-Chemical Studies of Catechins and Epicatechins
-
The physico-chemical properties of (-)-epicatechin, (+)-catechin have been found to be at variance from those reported in literature, and have been corrected after confirmation, by elemental analysis, TGA etc.A quasiracenate (C15H14O6*3H2O) of (-)-epicatechin and (+)-catechin (1 : 1) has also been isolated and characterised.
- Singh, Joginder,Ralhan, N. K.,Pant, T. K.
-
p. 1044 - 1047
(2007/10/02)
-
- Synthesis and Conformation of Procyanidin Diastereoisomers
-
The four theoretically possible diastereoisomeric 4->8 linked procyanidin dimers with two 2,3-cis-flavanoid units, epicatechin-(4β->8)-epicatechin (6), epicatechin-(4β->8)-ent-epicatechin (8), ent-epicatechin-(4α->8)-epicatechin (7), and ent-epicatechin-(4α->8)-ent-epicatechin (2), have been synthesized together with the 2,3-trans diastereoisomers catechin-(4α->8)-catechin (14) and catechin-(4α->8)-ent-catechin (15).The preferred rotamer conformations of the deca-acetate derivatives of (6), (8), (14), and (15) in chloroform were deduced from their 13C n.m.r. and high-field 1H n.m.r. spectra.The 1H n.m.r. spectra of the preferred conformers of the pairs of acetate derivatives of (6) and (15), and (8) and (14), were qualitatively similar as the relative configuration about the interflavanoid bond of one pair has a meso-relationship to the other.
- Foo, Lai Yeap,Porter, Lawrence J.
-
p. 1535 - 1543
(2007/10/02)
-
- FLAVANOL GLUCOSIDES FROM RHUBARB AND RHAPHIOLEPIS UMBELLATA
-
Investigations of rhubarb and the bark of Rhaphiolepis umbellata led to the isolation of new flavan-3-ol glucosides.Their structures were elucidated on the basis of 1H and 13C NMR analysis and hydrolytic studies as (+)-catechin 5-O-β-D-glucopyranoside and (-)-catechin 7-O-β-D-glucopyranoside.Key Word Index - Rhubarb; Polygonaceae; Rhaphiolepis umbellata; Rosaceae; flavan-3-ol glucosides; catechin.
- Nonaka, Gen-Ichiro,Ezaki, Emiko,Hayashi, Katsuya,Nishioka, Itsuo
-
p. 1659 - 1662
(2007/10/02)
-
- One-Electron Redox Potentials of Phenols. Hydroxy- and Aminophenols and Related Compounds of Biological Interest
-
The rate constants for reversible electron transfer between a series of substituted phenolate ions and anilines and various substituted phenoxyl or anilino radicals in aqueous solution were measured by observing the formation or depletion of the radicals involved.Nonequilibrium concentrations of the radicals were produced in the presence of the corresponding phenols or anilines by using the pulse radiolysis technique.The relaxation of the system to equilibrium was monitored by optical detection methods.From the equilibrium constants for one-electron transfer, the one-electron redox potentials (E2) for 38 phenolic or anilino type compounds were determined, many of which are natural products.The redox potentials are strongly influenced by electron-donating or -withdrawing substituents at the aromatic system.
- Steenken, S.,Neta, P.
-
p. 3661 - 3667
(2007/10/02)
-
- Kinetics of Epimerization of (+)-Catechin and Its Rearrangement to Catechinic Acid
-
The rates of epimerization of (+)-catechin (1) to (+)-epicatechin (2) and of (-)-epicatechin to (-)-catechin in aqueous solution were measuredthe pH range 5.4-11.0 and the temperature range 34-100 deg C.The rate of conversion of (+)-catechin to catechinic acid (3) also was measured under these conditions.First-order kinetics were observed for all three processes.At low pH, k(epimerization) >> k(rearrangement), and epimerization approached an equilibrium in which (+)-catechin predominated(+)-epicatechin.Near pH 11 and at elevated temperatures,k(epimerization) was only slightly greater than k(rearrangement), and the rapid, irreversible formation of catechinic acid under these conditions determined product composition.Both the epimerization of catechin and its rearrangement to catechinic acid can be rationalized in terms of a quinone methide intermediate (4).
- Kiatgrajai, Preecha,Wellons, J. D.,Gollob, Lawrence,White, James D.
-
p. 2910 - 2912
(2007/10/02)
-
- Flavanoids of Acacia catechu Heartwood
-
From the heartwood of Acacia catechu, kaempferol, dihydrokaempferol, taxifolin, isorhamnetin, (+)-afzelchin and a dimeric procyanidin (AC) have been isolated for the first time in addition to quercetin and (-)-epicatechin.
- Deshpandl, V. H.,Patil, A. D.
-
-