- Synthesis and antioxidant activity of a procyanidin B3 analogue
-
Proanthocyanidin, an oligomer of catechin, is a natural antioxidant and a potent inhibitor of lectin-like oxidized LDL receptor-1, which is involved in the pathogenesis of arteriosclerosis. We synthesized proanthocyanidin analogue 1, in which the geometry of one catechin molecule in procyanidin B3, a dimer of (+)-catechin, is constrained to be planar. The antioxidant activities of the compounds were evaluated in terms of their capacities to scavenge galvinoxyl radicals, and results demonstrate that while procyanidin was 3.8 times more potent than (+)-catechin, the radical scavenging activity of proanthocyanidin analogue 1 was further increased to 1.9 times that of procyanidin B3. This newly designed proanthocyanidin analogue 1 may be a promising lead compound for the treatment of arteriosclerosis and related cerebrovascular diseases.
- Mizuno, Mirei,Nakanishi, Ikuo,Matsubayashi, Satoko,Imai, Kohei,Arai, Takuya,Matsumoto, Ken-ichiro,Fukuhara, Kiyoshi
-
-
Read Online
- O-Benzylation of phloroglucinol via phloroglucinol triacetate
-
O-Benzylation of phloroglucinol, which was difficult due to C-benzylation, was successfully carried out by a method using phloroglucinol triacetate as an intermediate.
- Kawamoto, Haruo,Nakatsubo, Fumiaki,Murakami, Koji
-
-
Read Online
- COMPOSITION FOR ENHANCING SKIN ELASTICITY OR IMPROVING SKIN WRINKLES COMPRISING HEPTAHYDROXYFLAVAN AS AN EFFECTIVE INGREDIENT
-
Heptahydroxyflavan or a salt, isomer, hydrate or solvate thereof, which is an active ingredient of the present disclosure, can enhance skin elasticity and improve skin wrinkles by inhibiting the activity of MMP-1. In addition, the heptahydroxyflavan or a salt, isomer, hydrate or solvate thereof, which is an active ingredient of the present disclosure, can be used in various compositions such as cosmetics, health functional foods, etc. because it is safe with no cytotoxicity.
- -
-
Paragraph 0045
(2021/01/26)
-
- Total Synthesis of the Natural Products Ulmoside A and (2 R,3 R)-Taxifolin-6- C -β- d -glucopyranoside
-
An efficient first total synthesis of highly polar ulmoside A and (2 R,3 R)-taxifolin-6- C -β- d -glucopyranoside, useful for the prevention of metabolic disorders, has been described. Key elements of the synthesis include a Sc(OTf) 3-catalyzed regio- and stereoselective C -glycosidation on taxifolin in 35percent yield with d -glucose and chiral semipreparative reverse-phase high-performance liquid chromatography (HPLC) for the separation of both taxifolins and the diastereomeric mixture of taxifolin-6- C -β- d -glucopyranosides. Correlation of the analytical data of synthetic ulmoside A and its diastereomer with a natural ulmoside A sample confirmed the assigned absolute stereochemistry of the natural products.
- Batchu, Venkateswara Rao,Dorigundla, Aravind Reddy,Gurrapu, Raju,Macha, Lingamurthy,Vanka, Umamaheswara Sarma
-
supporting information
p. 1097 - 1101
(2020/07/03)
-
- Molecular Mechanism by Which Tea Catechins Decrease the Micellar Solubility of Cholesterol
-
Tea polyphenols lower the levels of cholesterol in the blood by decreasing the cholesterol micellar solubility. To clarify this mechanism, the interactions between taurocholic acid and (-)-epigallocatechin gallate (EGCg) and its derivatives were investigated. 13C NMR studies revealed remarkable chemical-shift changes for the carbonyl carbon atom and the 1″- and 4″-positions in the galloyl moiety. Furthermore, 1H NMR studies using (-)-EGCg derivatives showed that the number of hydroxyl groups on the B ring did not affect these interactions, whereas the carbonyl carbon atom and the aromatic ring of the galloyl moiety had remarkable effects. The configuration at the 2- and 3-positions of the catechin also influenced these interactions, with the trans-configuration resulting in stronger inhibition activity than the cis-configuration. Additionally, a 1:1 component ratio for the catechin-taurocholic acid complex was determined by electrospray ionization-mass spectrometry. These molecular mechanisms contribute to the development of cholesterol-absorption inhibitors.
- Sakakibara, Takumi,Sawada, Yoshiharu,Wang, Jilite,Nagaoka, Satoshi,Yanase, Emiko
-
-
- Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin
-
Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocyanidin derivatives with more potent antioxidative activity and stronger inhibition for LOX-1 demonstrated the synthesis of a novel proanthocyanidin derivative (1), in which the geometry of one catechin molecule in procyanidin B3 was constrained to a planar orientation. The radical scavenging activity of 1 was 1.9-fold higher than that of procyanidin B3. Herein, we synthesized another procyanidin B3 analogue (2), in which the geometries of both catechin molecules in the dimer were constrained to planar orientations. The radical scavenging activity of 2 was 1.5-fold higher than that of 1, suggesting that 2 may be a more effective candidate than 1 as a therapeutic agent to reduce oxidative stress induced in arteriosclerosis or related cerebrovascular disease.
- Mizuno, Mirei,Nakanishi, Ikuo,Matsumoto, Ken-ichiro,Fukuhara, Kiyoshi
-
p. 5010 - 5013
(2017/10/24)
-
- NOVEL ANALOGUES OF EPICATECHIN AND RELATED POLYPHENOLS
-
The present invention provides novel analogues of epicatechin and related polyphenols, their variously functionalized derivatives, process for preparation of the same, composition comprising these compounds and their method of use.
- -
-
Paragraph 0144; 0145
(2016/03/05)
-
- Synthesis method of procyanidine compound Catechin
-
The invention relates to a synthesis method of a procyanidine compound Catechin and belongs to the field of chemical synthesis. The method is as below: conducting benzyl protection reaction on trans-caffeic acid to produce O-Bz caffeic acid; subjecting O-Bz caffeic acid to an ester reduction reaction for synthesis of allyl alcohol; subjecting allyl alcohol to a Sharpless dihydroxylation reaction to synthesize a trihydroxy compound; subjecting the trihydroxy compound to a selective sulfonylation reaction to synthesize sulfonate; subjecting the sulfonate to an O-Ts leaving reaction to synthesize ternary epoxy; conducting a hydroxy mitsunobu reaction to synthesiz O-Ph epoxy; subjecting O-Ph epoxy to a ring-forming reaction to synthesize O-Bz Catechi; subjecting O-Bz Catechin to a palladium carbon deprotection reaction to synthesize the procyanidine compound Catechin (shown in figure). The invention has the characteristics of few reaction steps, high total yield, good product selectivity, and suitability for industrial production.
- -
-
-
- 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.
- -
-
Paragraph 0156; 0157; 0158
(2016/01/15)
-
- The flavan-isoflavan rearrangement: Bioinspired synthetic access to isoflavonoids via 1,2-shift-alkylation sequence
-
An approach to 2-substituted isoflavonoids is reported based on the 1,2-shift of the aryl group in the catechin skeleton followed by the in situ alkylation. Synthesis of (-)-equol, a natural isoflavan with estrogenic activities, was achieved.
- Nakamura, Kayo,Ohmori, Ken,Suzuki, Keisuke
-
supporting information
p. 7012 - 7014
(2015/04/22)
-
- FLAVONOID COMPOUNDS
-
The present invention relates to compounds, compositions, and methods for treatment of conditions related to mitochondrial function. In various aspects, the present invention comprises administering one or more epicatechin derivatives in an amount effective to stimulate mitochondrial function in cells. The compounds, compositions, and methods described herein provide for reducing infarct size in the heart following permanent ischemia or ischemia/reperfusion event or method for delaying, attenuating or preventing adverse cardiac remodeling, and can assist in prevention of impaired mitochondria biogenesis and thus prevention of the consequences of impaired mitochondrial biogenesis in various diseases and conditions, as well as provide for the active therapy of mitochondrial depletion that may have already occurred.
- -
-
Paragraph 0436-0439
(2014/09/29)
-
- Design, synthesis and characterization of novel inhibitors against mycobacterial β-ketoacyl CoA reductase FabG4
-
We report the design and synthesis of triazole-polyphenol hybrid compounds 1 and 2 as inhibitors of the FabG4 (Rv0242c) enzyme of Mycobacterium tuberculosis for the first time. A major advance in this field occurred only a couple of years ago with the X-ray crystal structure of FabG4, which has helped us to design these inhibitors by the computational fragment-based drug design (FBDD) approach. Compound 1 has shown competitive inhibition with an inhibition constant (Ki) value of 3.97 ± 0.02 μM. On the other hand, compound 2 has been found to be a mixed type inhibitor with a Ki value of 0.88 ± 0.01 μM. Thermodynamic analysis using isothermal titration calorimetry (ITC) reveals that both inhibitors bind at the NADH co-factor binding domain. Their MIC values, as determined by resazurin assay against M. smegmatis, indicated their good anti-mycobacterial properties. A preliminary structure-activity relationship (SAR) study supports the design of these inhibitors. These compounds may be possible candidates as lead compounds for alternate anti-tubercular drugs. All of the reductase enzymes of the Mycobacterium family have a similar ketoacyl reductase (KAR) domain. Hence, this work may be extrapolated to find structure-based inhibitors of other reductase enzymes. The Royal Society of Chemistry.
- Banerjee, Deb Ranjan,Dutta, Debajyoti,Saha, Baisakhee,Bhattacharyya, Sudipta,Senapati, Kalyan,Das, Amit K.,Basak, Amit
-
-
- Factors influencing the antifolate activity of synthetic tea-derived catechins
-
Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.
- Saez-Ayala, Magali,Fernandez-Perez, Maria Piedad,Chazarra, Soledad,McHedlishvili, Nani,Tarraga-Tomas, Alberto,Rodriguez-Lopez, Jose Neptuno
-
p. 8319 - 8341
(2013/08/23)
-
- Unified approach to catechin hetero-oligomers: First total synthesis of trimer EZ-EG-CA isolated from Ziziphus jujuba
-
A catechin hetero-trimer isolated from Ziziphus jujuba has been synthesized. Among three constituent monomers, (-)-epiafzelechin and (-)-epigallocatechin were prepared by de novo synthesis. Trimer formation relied on the unified approach to oligomers based on the bromo-capping and the orthogonal activation, reaching the reported structure of the natural product. The Royal Society of Chemistry 2012.
- Yano, Takahisa,Ohmori, Ken,Takahashi, Haruko,Kusumi, Takenori,Suzuki, Keisuke
-
supporting information
p. 7685 - 7688
(2013/04/23)
-
- Procyanidin oligomers. A new method for 4→8 interflavan bond formation using C8-boronic acids and iterative oligomer synthesis through a boron-protection strategy
-
Interest in the synthesis of procyanidin (catechin or epicatechin) oligomers that contain the 4→8 interflavan linkage remains high, principally due to research into their health effects. A novel coupling utilising a C8-boronic acid as a directing group was developed in the synthesis of natural procyanidin B3 (i.e., 3,4-trans-(+)-catechin-4α→8-(+)- catechin dimer). The key interflavan bond was forged using a novel Lewis acid-promoted coupling of C4-ether 6 with C8-boronic acid 16 to provide the α-linked dimer with high diastereoselectivity. Through the use of a boron protecting group, the new coupling procedure was extended to the synthesis of a protected procyanidin trimer analogous to natural procyanidin C2.
- Dennis, Eric G.,Jeffery, David W.,Johnston, Martin R.,Perkins, Michael V.,Smith, Paul A.
-
experimental part
p. 340 - 348
(2012/01/06)
-
- Comparison of a Pair of Synthetic Tea-Catechin-Derived Epimers: Synthesis, Antifolate Activity, and Tyrosinase-Mediated Activation in Melanoma
-
Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to improve the stability and cellular absorption of tea polyphenols. The antiproliferative and pro-apoptotic activities of both compounds were analyzed with various cancer cell systems, and TMCG, which was easily synthesized in excellent yield, was more active than TMECG in both melanoma and non-melanoma cell lines. TMCG was also a better inhibitor of dihydrofolate reductase and was more efficiently oxidized by tyrosinase, potentially explaining the difference in activity between these epimers.
- Saez-Ayala, Magali,Sanchez-Del-Campo, Luis,Montenegro, Maria F.,Chazarra, Soledad,Tarraga, Alberto,Cabezas-Herrera, Juan,Rodriguez-Lopez, Jose Neptuno
-
scheme or table
p. 440 - 449
(2012/01/06)
-
- Synthesis and antimicrobial activities of 3-O-alkyl analogues of (+)-catechin: Improvement of stability and proposed action mechanism
-
We report here the synthesis and biological properties of 3-O-alkyl analogues of (+)-catechin (5), which itself is one of the major natural polyphenols found in green tea and has several physiological activities. Starting from 5, a series of 3-O-alkyl-(+)-catechin derivatives were investigated as potent antimicrobial agents. The presence of an alkyl chain rather than acyl on 3-O- showed an increase in antimicrobial activity which may be due to stability in standard culture condition. The most promising compound is 8e, 3-O-decyl analogue, with the MIC of 0.5-2, 32-128 and 2-4?μg/mL against Gram-positive bacteria, Gram-negative bacteria and human pathogenic fungi, respectively. Regarding action mechanism, the antimicrobial activity is possibly due to the lipophilicity and disrupting ability of the analogues to the liposome membrane.
- Park, Ki Duk,Cho, Sung Jin
-
experimental part
p. 1028 - 1033
(2010/04/24)
-
- Synthesis and ribonuclease A inhibition activity of resorcinol and phloroglucinol derivatives of catechin and epicatechin: Importance of hydroxyl groups
-
The reported ribonuclease A inhibitory activity of the green tea extracts prompted us to synthesize novel catechin/epicatechin based conjugates with resorcinol and phloroglucinol with the aim to increase the number of phenolic OH groups. These are found to be more effective inhibitors of ribonuclease A as compared to catechin and epicatechin thus indicating the importance of number of phenolic OH groups for the inhibition of ribonucleolytic activity. Fluorescence studies have been carried out to evaluate the binding parameters. The protein-ligand docking studies are also performed to gain insight into the protein-polyphenols interactions. The epicatechin based polyphenols 1 and 2 also showed inhibition of angiogenin-induced angiogenesis, as determined by chorioallantoic membrane (CAM) assay.
- Dutta, Sansa,Basak, Amit,Dasgupta, Swagata
-
scheme or table
p. 6538 - 6546
(2010/10/03)
-
- Total synthesis of 14C-labeled procyanidin B2
-
During the last decades, many in vitro and in vivo studies have shown the beneficial effects on health of procyanidins. However, their absorption and metabolism is still not fully understood and some aspects are still controversial. In order to have a clearer picture of the metabolism of procyanidins, the use of labelled compounds is essential. In this context, the enantioselective synthesis of 14C-radiolabelled procyanidin B2 was developed in our laboratories. It was achieved in fourteen 'hot' steps, involving as key steps the Sharpless dihydroxylation of an elaborated alkene, a stereoselective intramolecular cyclization to benzylated (+)-catechin and the condensation of two (-)-epicatechin units. 11 mCi of protected procyanidin B2 were obtained from 524 mCi of potassium [14C]cyanide. Copyright
- Viton, Florian,Landreau, Cyrille,Rustidge, David,Little, Gill,Robert, Fabien,Williamson, Gary,Barron, Denis
-
p. 371 - 374
(2011/05/05)
-
- Stereoselective synthesis of benzylated prodelphinidins and their diastereomers with use of the mitsunobu reaction in the preparation of their gallocatechin precursors
-
The tetrabenzylated catechin 9 was prepared by benzylation of the commercially available pure (+)-catechin (3) and cou-pled with the commercially unavailable pentabenzylated (-)-gallocatechin 10, prepared in a one-step Mitsunobu-type cyclization of the triol 8. The highly stereoselective synthesis of benzylated prodelphinidins - catechin-(4α→8)-gallocate-chin (13), gallocatechin-(4α→8)-gallocatechin (14), and gallo-catechin- (4α→8)-catechin (15) - is reported for the first time. The ESI(+)-CID mass spectra of the coupling products were found to feature regioselective retro-Diels-Alder (RDA) reac-tions and unusual sequential losses of pairs of C7H7' radicals (182 u) from the Na+ adduct ions.
- Krohn, Karsten,Ahmed, Ishtiaq,John, Markus,Letzel, Matthias C.,Kuck, Dietmar
-
experimental part
p. 2544 - 2554
(2010/09/05)
-
- Synthesis of procyanidins by stepwise- and self-condensation using 3,4-cis-4-acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-ben zyl-(+)-catechin and (-)-epicatechin as a key building monomer
-
3,4-cis-4-Acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-ben zyl-(+)-catechin (1a) or (-)-epicatechin (1b) reacted high regio- and stereo-selectively with 1.5 equiv of the 5,7,3′,4′-tetra-O-benzyloxyflavan-3-ol (4a or 4b) in the presence of 1 equiv of TMSOTf to give the corresponding procyanidins. On the other hand, the self-condensation of 1a in the presence of a catalytic amount of B(C6F5)3 afforded wide-range procyanidins from dimer to 15-mer like a biomass.
- Oyama, Kin-ichi,Kuwano, Miyuki,Ito, Mie,Yoshida, Kumi,Kondo, Tadao
-
p. 3176 - 3180
(2008/09/20)
-
- Synthesis and biological activity of a 3,4,5-trimethoxybenzoyl ester analogue of epicatechin-3-gallate
-
Despite presenting bioavailability problems, tea catechins have emerged as promising chemopreventive agents because of their observed efficacy in various animal models. To improve the stability and cellular absorption of tea polyphenols, we developed a new catechin-derived compound, 3-O-(3,4,5- trimethoxybenzoyl)-(-)-epicatechin (TMECG), which has shown significant antiproliferative activity against several cancer cell lines, especially melanoma. The presence of methoxy groups in its ester-bound gallyl moiety drastically decreased its antioxidant and prooxidant properties without affecting its cell-antiproliferative effects, and the data indicated that the 3-gallyl moiety was essential for its biological activity. As regards its action mechanism, we demonstrated that TMECG binds efficiently to human dihydrofolate reductase and downregulates folate cycle gene expression in melanoma cells. Disruption of the folate cycle by TMECG is a plausible explanation for its observed biological effects and suggests that, like other antifolate compounds, TMECG could be of clinical value in cancer therapy.
- Sánchez-del-Campo, Luís,Otón, Francisco,Tárraga, Alberto,Cabezas-Herrera, Juan,Chazarra, Soledad,Rodríguez-López, José Neptuno
-
p. 2018 - 2026
(2008/09/20)
-
- First total synthesis of14C-labeled procyanidin B2 - A milestone toward understanding cocoa polyphenol metabolism
-
The idea that foods consumed for pure pleasure could provide health benefits received much recognition in the recent years. Among these foods, cocoa and dark chocolate are particularly rich in procyanidins, one of the major dietary families of polyphenols. We developed the first asymmetric total synthesis of procyanidin B2 and applied it to the preparation of a regioselectively radiolabeled 14C-analogue, which will be used to strengthen our knowledge on the metabolism of procyanidins. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Viton, Florian,Landreau, Cyrille,Rustidge, David,Robert, Fabien,Williamson, Gary,Barron, Denis
-
supporting information; experimental part
p. 6069 - 6078
(2009/05/27)
-
- Processes for the preparation of protected-(+)-catechin and (-)-epicatechin monomers, for coupling the protected monomers with an activated, protected epicatechin monomer, and for the preparation of epicatechin-(4B,8)-epicatechin or -catechin dimers and their digallates
-
Improved processes for the preparation of tetra-O-benzyl protected catechin, for the coupling of the tetra-O-benzyl protected catechin or epicatechin with a C-4 activated, tetra-O-benzyl protected epicatechin for the galloylation of the epicatechin-(4β,8)-catechin or -epicatechin dimer-the dimer digallates, and for the deprotection (i.e., debenzylation) of the protected epicatechin dimers and protected epicatechin dimer digallates are disclosed.
- -
-
Page/Page column 2-3
(2010/11/25)
-
- 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 27-28
(2010/11/25)
-
- Scale-Up Syntheses of Two Naturally Occurring Procyanidins: (-)-Epicatechin-(4β,8)-(+)-catechin and (-)-Epicatechin-3-0-galloyl- (4β, 8)-(-)-epicatechin-3-0-gallate
-
A scaleable process for the synthesis of two naturally occurring procyanidins, namely (-)-epicatechin-(4β,8)-(+)-catechin (1) and(-)-epiratechin-3-O-galloyl-(4β,8)-(-)-epicatechin-3-O-gallate (2), is described. The key steps were highlighted by improvements for the benzylation of (+)-catechin (3), stereo-selective reduction of the C-3 keto group of (2A)-5,7,3′,4′-tetrakis(benzyloxy)flavan-3-one (10), and coupling between 4-hydroxyethoxy-5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (11) and 5,7,3′,4′-tetra-O-benzyl-(+)-catechin (4) or 5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (6), respectively. The debenzylation performed in a biphasic system resulted in an improved yield and purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds (1 and 2) for various in vitro, ex vivo, and in vivo studies. Moreover, the scale-up process provided a detailed description for the preparation of multihundred to kilogram scale quantities of intermediates used in the synthesis of these two titled procyanidins.
- Sharma, Pradeep K.,Kolchinski, Alexander,Shea, Helene A.,Nair, Jayesh J.,Gou, Yanni,Romanczyk Jr., Leo J.,Schmitz, Harold H.
-
p. 422 - 430
(2012/12/31)
-
- Analysis of benzylation products of (+)-catechin
-
Catechin, a flavanol compound from tea leaves, is one of useful starting materials in many synthetic studies toward various flavonoids. For synthesis, benzyl group is frequently chosen for protecting phenolic hydroxyl groups. To clarify the reactivity of each hydroxyl groups of catechin and realize an efficient reaction condition, we analyzed the products of the benzylation reaction of (+)-catechin. Two known and five new compounds were purified from the reaction mixture and their structure was determined. Not only O-benzylated products, but also 6 and/or 8-C-benzylated compounds were obtained. However, 3-OH group was never benzylated in this reaction.
- Nakamura, Saki,Oyama, Kin-ichi,Kondo, Tadao,Yoshida, Kumi
-
experimental part
p. 451 - 460
(2009/09/08)
-
- An improved synthesis of procyanidin dimers: Regio- and stereocontrol of the interflavan bond
-
A direct and general synthesis of procyanidin dimers B1, B2, B3 and B4 (10a-d) is presented. The approach is based on the stoichiometric coupling of two protected monomeric units (the nucleophilic 2a-b and electrophilic 4a-b partners) and deals with the regio- and stereocontrol of the C4-C8 interflavan bond as well as the control of the degree of oligomerization. The synthesis involves a five-step pathway starting from the native catechin (1a) or epicatechin (1b) to the fully deprotected dimers 10a-d. Furthermore, the process appears to be iterative as the coupling intermediates 9a-d themselves can be readily used in further selective syntheses of trimers or higher oligomers. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Tarascou, Isabelle,Barathieu, Karine,Andre, Yann,Pianet, Isabelle,Dufourc, Erick J.,Fouquet, Eric
-
p. 5367 - 5377
(2007/10/03)
-
- Influence of an 8-trifluoroacetyl group on flavanol couplings
-
The effect of an electron attracting substituent in the Lewis acid catalyzed oligomerization of flavanols was investigated. The results showed that the presence of a COCF3, at the 8 position of a (+)-catechin unit strongly influenced the attack of the 6 free nucleophile flavanol position by the electrophile generated from a 4-O-alkyloxy protected catechin unit. This was observed either with TiCl4 or TMSOTf as Lewis acids in which the carbon-carbon bond formation was inhibited and the corresponding dimer was detected in small amount. On the contrary, the formation of a carbon-oxygen bond was observed and the corresponding C-4→O→C-3 ether linked procyanidin dimer was isolated in a good yield. In order to avoid the participation of the C-3 hydroxyl group in the dimerization reaction, the two flavanol units were forced into C-4→C-8 coupling by use of an internal link. The structural elucidation of the isolated compounds was achieved through MS and NMR spectroscopy.
- Es-Safi, Nour-Eddine,Le Guernevé, Christine,Kerhoas, Lucien,Ducrot, Paul-Henri
-
p. 2705 - 2714
(2007/10/03)
-
- Synthesis and preliminary anticancer activity studies of C4 and C8-modified derivatives of catechin gallate (CG) and epicatechin gallate (ECG)
-
We have developed an improved and reliable method for stereoselective functionalization at C4 of naturally occurring (+)-catechin. Our method utilizes DDQ oxidation followed by trapping of the quinonemethide intermediate with allyl alcohol. The quinonemethide intermediate can be regenerated from the allyl ether by exposure to boron trifluoride diethyl etherate. This reactive intermediate can be trapped with a wide range of external nucleophiles. NBS bromination, lithium halogen exchange, and alkylation gave access to C8-allyl derivatives of (+)-catechin, and this allyl group was used in a series of cross-metathesis experiments to prepare novel dimeric catechin-derived products. Gallate ester derivatives of the novel C4- and C8-substituted catechins were prepared, and these materials were screened for potential anticancer activity in a range of human cancer cell lines. From these preliminary cytotoxicity assays (MTT) we found that C8-propyl-catechin gallate was more active (IC50 = 31 μM) than catechin gallate (CG, IC50 = 53 μM) or epicatechin gallate (ECG, IC50 = 76 μM) against the colorectal adenocarcinoma cell line HCT116. Differential sensitivity in pancreas (Pan1), bladder (RT112), stomach (MGLVA1), liver (HepG2), and fibroblasts (46Br.1G1) cell lines was also observed.
- Hayes, Christopher J.,Whittaker, Benjamin P.,Watson, Susan A.,Grabowska, Anna M.
-
p. 9701 - 9712
(2007/10/03)
-
- Hydroxylation of ring A of flavan-3-ols: Influence of the ring A substitution pattern on the oxidative rearrangement of 6-hydroxyflavan-3-ols
-
A general procedure for the oxidation of catechin derivatives is described, leading to the introduction of a new hydroxyl group at C-6. This procedure has been used for the synthesis of a number of 6-hydroxy flavan-3-ols, including elephantorrhizol, a natural flavan-3-ol exhibiting a fully substituted A ring. The substitution at C-8, albeit of poor influence on the course of this oxidation reaction, has been demonstrated to be preponderant for the further spontaneous oxidation and rearrangement of 6-hydroxy-flavan-3-ols into p-benzoquinones. The whole procedure allows the preparation of 6-alkyl substituted benzoquinones derived from catechin. Georg Thieme Verlag Stuttgart.
- Boyer, Francois-Didier,Beauhaire, Josiane,Martin, Marie Therese,Ducrot, Paul-Henri
-
p. 3250 - 3260
(2008/09/16)
-
- Synthesis of modified proanthocyanidins: Introduction of acyl substituents at C-8 of catechin. Selective synthesis of a C-4 → O → C-3 ether-linked procyanidin-like dimer
-
The regioselective introduction of substituents at C-8 of (+)-catechin is described, leading to the synthesis of several catechin derivatives with various substitution patterns to be used for the further synthesis of modified proanthocyanidins. Thereafter, a new 3-O-4 ether-linked procyanidin-like derivative was synthesized. Its formation was selectively achieved through TiCl4-catalyzed condensation of 4-(2-hydroxyethoxy)tetra-O-benzyl catechin with the 8-trifluoroacetyl adduct of tetra-O-benzyl catechin.
- Beauhaire, Josiane,Es-Safi, Nour-Eddine,Boyer, Francois-Didier,Kerhoas, Lucien,Le Guerneve, Christine,Ducrot, Paul-Henri
-
p. 559 - 562
(2007/10/03)
-
- Compositions and methods of use of dimer digallates
-
The invention relates to compositions, such as pharmaceuticals, foods, food additives, or dietary supplements, containing dimer digallates, and methods of use thereof, for prophylactic or therapeutic treatment of a human or a veterinary animal to treat or prevent NO-responsive health conditions, treat hypertension, cardiovascular disease, coronary artery disease, diabetes, cognitive dysfunction or disorder and/or vascular circulation disorders, prevent or reduce the risk of heart attack, stroke, congestive heart failure and/or kidney failure, or to improve blood flow, for example renal blood flow. The composition may optionally contain an additional NO modulating agent and/or a vascular-protective or therapeutic agent, or may be administered in combination with such an agent.
- -
-
Page/Page column 12
(2010/02/15)
-
- Study of the green tea polyphenols catechin-3-gallate (CG) and epicatechin-3-gallate (ECG) as proteasome inhibitors
-
The green tea polyphenol catechin-3-gallate (CG) and epicatechin-3-gallate (ECG) were synthesized enantioselectively via a Sharpless hydroxylation reaction followed by a diastereoselective cyclization. Their potencies to inhibit the proteasome activity were measured. The unnatural enantiomers were found to be equally potent to the natural compounds.
- Wan, Sheng Biao,Chen, Di,Dou, Q. Ping,Chan, Tak Hang
-
p. 3521 - 3527
(2007/10/03)
-
- Methods in synthesis of flavonoids. Part 2: High yield access to both enantiomers of catechin
-
Resolution of racemic synthetic tetra-O-benzylcatechin 2 is described, through the formation of esters S and 6 derived from dibenzoyl-L-tartaric acid. The diastereoisomer of the natural series 6 was separated by crystallization, the other one being an oil. This process allowed us to prepare enantiomerically pure (+)-catechin 8 in high yield. The pure isomer in the ent-series 9 could be obtained, following the same scheme of reactions. (C) 2000 Elsevier Science Ltd.
- Nay,Monti,Nuhrich,Deffieux,Merillon,Vercauteren
-
p. 9049 - 9051
(2007/10/03)
-
- Studies in polyphenol chemistry and bioactivity. 1. Preparation of building blocks from (+)-catechin. Procyanidin formation. Synthesis of the cancer cell growth inhibitor, 3-O-galloyl-(2R,3R)-epicatechin-4β,8-[3-O-galloyl-(2R,3R)-epicatechin]
-
A project has been initiated to synthesize proanthocyanidin oligomers found in cocoa. Natural, readily available (+)-catechin was transformed into 5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (14) by (a) benzylation of the phenolic oxygens; (b) oxidation of the 3-alcohol to ketone by the Dess-Martin periodinane; and (c) reduction with lithium tri-sec-butylborohydride (L-Selectride) in the presence of LiBr. The additive diminishes the extent of ketone enolization while maintaining a stereoselectivity of ≥ 200:1. Oxidation of 14 with DDQ was performed best from the standpoint of product purification if ethylene glycol was used as the nucleophilic trapping agent. The resulting ether 19 was condensed with 14 using TiCl4 to give a good yield of benzyl-protected epicatechin-4β,8-epicatechin (octa-O-benzylprocyanidin B2, 20) as the sole dimeric product. Hydrogenolysis of 20 yielded procyanidin B2 in the first enantiospecific synthesis of this natural product which employs protected intermediates and thereby allows the necessary product separation after the condensation step to be performed on nonpolar, nonsensitive intermediates. Acylation of 20 with tri-O-benzylgalloyl chloride followed by hydrogenolysis gave access to the title bis-gallate (24). This constitutes the first synthesis of this natural product, a compound notable for its PKC-inhibitory and anticancer activity.
- Tueckmantel, Werner,Kozikowski, Alan P.,Romanczyk Jr., Leo J.
-
p. 12073 - 12081
(2007/10/03)
-