490-46-0

Basic information

• Product Name: L-Epicatechin
• Synonyms: (-)-EPICATECHIN;(+)-EPICATECHIN;EPICATECHIN;EPICATECHIN, (-)-;EPICATECHIN, (+)-;CIS-2-[3,4-DIHYDROXYPHENYL]-3,4-DIHYDRO-2H-1-BENZOPYRAN-3,5,7-TRIOL;(-)-CIS-3,3',4',5,7-PENTAHYDROXYFLAVANE;CIS-3,3',4',5,7-PENTAHYDROXYFLAVANE
• CAS NO: 490-46-0
• Molecular Formula: C₁₅H₁₄O₆
• Molecular Weight: 290.27
• EINECS: 207-710-1
• Product Categories: Pharmaceutical Raw Materials;chiral;Aromatics;Chiral Reagents;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract
• Mol File: 490-46-0.mol

Chemical Properties

• Melting Point: 240 °C (dec.)(lit.)
• Boiling Point: 630.4 °C at 760 mmHg
• Flash Point: 335°C
• Appearance: White to light yellow crystal powder
• Density: 1.593g/cm³
• Storage Temp.: 2-8°C
• Solubility: insoluble in H2O; insoluble in EtOH; ≥14.5 mg/mL in DMSO
• PKA: 9.54±0.10(Predicted)
• Water Solubility: Soluble in water or alcohol
• Merck: 13,1912
• BRN: 92760
• CAS DataBase Reference: L-Epicatechin(CAS DataBase Reference)
• NIST Chemistry Reference: L-Epicatechin(490-46-0)
• EPA Substance Registry System: L-Epicatechin(490-46-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: KB3745000
• F: 10-23
• Hazardous Substances Data: 490-46-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
L-Epicatechin is used as an antioxidant and natural product from green tea for its potent antioxidant properties, which are more effective than ascorbate or α-tocopherol in certain in vitro lipid peroxidation assays. It inhibits cyclooxygenase 1 (IC50 = 3.2 μM) and acts synergistically with epigallocatechin gallate to induce apoptosis in, and reduce the proliferation of, PC-9 lung cancer cells when used at a concentration of 200 μM.
Used in Nutraceutical Applications:
L-Epicatechin is used as a nutraceutical ingredient for its health-promoting properties, including its ability to scavenge DPPH radicals in a cell-free assay when used at a concentration of 5 μM. It also reduces LPS-induced increases in plasma creatinine and urea levels in a rat model of renal inflammation when administered at a dosage of 80 mg/kg.
Used in Food and Beverage Industry:
L-Epicatechin is used as an additive in the food and beverage industry for its antioxidant properties, which help in preserving the freshness and quality of the products. It is abundantly present in cacao and cacao products, contributing to their health benefits and unique flavor profile.
Used in Cosmetics Industry:
L-Epicatechin is used as an active ingredient in the cosmetics industry for its antioxidant and anti-inflammatory properties. It can be incorporated into skincare products to help protect the skin from environmental stressors and promote a healthy, youthful appearance.

Biochem/physiol Actions

This antioxidant is found in chocolate. (-)-Epicatechin is linked with cardiovascular effects. It is considered as a dependable standard due to its availability in cacao seeds and cocoa products. The halogenating activity of myeloperoxidase can be restored by (-)-epicatechin.

references

[1]. chakravarthy bk, gupta s, gambhir ss, et al. pancreatic beta-cell regeneration in rats by (-)-epicatechin. lancet, 1981, 2(8249): 759-760.[2]. wippel r, rehn m, gorren ac, et al. interference of the polyphenol epicatechin with the biological chemistry of nitric oxide- and peroxynitrite-mediated reactions. biochem pharmacol, 2004, 67(7): 1285-1295.[3]. brossette t, hundsd?rfer c, kr?ncke kd, et al. direct evidence that (-)-epicatechin increases nitric oxide levels in human endothelial cells. eur j nutr, 2011, 50(7): 595-599.[4]. okushio k, suzuki m, matsumoto n, et al. identification of (-)-epicatechin metabolites and their metabolic fate in the rat. drug metab dispos, 1999, 27(2): 309-316.

InChI:InChI=1/C15H14O6/c16-8-4-11(18)9-6-13(20)15(21-14(9)5-8)7-1-2-10(17)12(19)3-7/h1-5,13,15-20H,6H2/t13-,15-/m1/s1

Synthetic route

(+/-)-epicatechin (154-23-4, 490-46-0, 7295-85-4, 13392-26-2, 17334-50-8, 18829-70-4, 35323-91-2, 72690-97-2) → (+)-epicatechin (35323-91-2) + (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0)

Conditions	Yield
With CHIRAL PAKIC In ethanol; hexane at 20℃; Resolution of racemate;	A 85% B 84%
With CHIRAL PAK IC (250 X 4.6) mm, 5μ column In methanol at 25℃; Product distribution / selectivity; Resolution of racemate;
With CHIRAL PAK In methanol at 25℃; Resolution of racemate;

5,7,3',4'-tetra-O-benzylepicatechin (87292-49-7) → (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0)

Conditions	Yield
With 5% Pd(OH)2/C; hydrogen In tetrahydrofuran; methanol; water at 20℃; for 0.5h;	69%
With hydrogen; palladium(II) hydroxide In ethyl acetate at 20℃; for 40h;
With hydrogen; palladium(II) hydroxide In ethyl acetate at 20℃; for 40h;	0.010 mg

C50H42O6 → (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0) + catechin (154-23-4)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol; ethyl acetate at 20 - 55℃;	A 55% B n/a

(-)-epicatechin gallate (863-03-6, 10517-25-6, 13445-34-6, 17431-25-3, 20819-16-3, 25615-05-8, 130405-40-2, 1257-08-5) → (-)-(2R,3R,4R)-3,4,5,7,3',4'-hexahydroxyflavan + (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0)

Conditions	Yield
With Diaporthe sp In methanol at 27℃; for 24h;	A 53% B 13%

procyanidin B1 (20315-25-7) → (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0) + catechin (154-23-4)

Conditions	Yield
With sodium cyanoborohydride In trifluoroacetic acid at 0℃; for 1h; Title compound not separated from byproducts;	A 21% B 20%

procyanidin B2 (29106-49-8) → (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol (490-46-0)

Conditions	Yield
With hydrogenchloride for 0.5h; heating on a boiling water bath;
Multi-step reaction with 2 steps 1: ethanol / 1 h / boiling water bath 2: Raney nickel / ethanol / 2 h / Ambient temperature View Scheme

Upstream product

• 29106-49-8 procyanidin B₂ 
• 23567-23-9 procyanidin B₃ 
• 29106-51-2 procyanidin B₄ 
• 88038-12-4 Cinnamtannin B₁ 
• 88057-90-3 epicatechin-(4β->8)-epicatechin-(4β->8)-epicatechin-(4β->8,2β->O->7)-epicatechin-(4α->8)-epicatechin 
• 88082-60-4 cinnamtannin B-1 
• 114715-49-0 (epi)afzelechin‐(4‐8)‐(epi)catechin 
• 79199-56-7 gallocatechin-(4α->8)-epicatechin 
• 97775-90-1 Camelliatannin A 
• 88038-15-7 epicatechin-(4β->6)-epicatechin-(2β->O->7, 4β->8)-epicatechin-(4β->8)-epicatechin 
• 68-11-1 mercaptoacetic acid 
• 82916-01-6 proanthocyanidin B₆ 
• 108907-44-4 (-)-(2R,3R)-5,7-dihydroxy-2-(3',4'-dihydroxy-phenyl)chroman-3-yl 3'',5''-dihydroxy-4''-methoxybenzoate 
• 103303-00-0 (-)-epi-catechin 3-O-β-D-glucopyranoside 

Downstream Products

• 37064-32-7 5,7,3',4'-tetra-O-methylepicatechin-4β,8-(5,7,3',4'-tetra-O-methylepicatechin) 
• 105561-65-7 octa-O-methylprocyanidin B-5 
• 85022-67-9 cinchonain Id 
• 85022-69-1 epicatechin-(7,8-bc)-4α-(3,4-dihydroxyphenyl)-dihydro-2(3H)-pyranone 
• 78306-10-2 (2R,3S,4R)-2,3-trans-3,4-cis-3,3',4',7-tetrahydroxy-4-<(2R,3R)-2,3-cis-3,3',4',5,7-pentahydroxyflavan-8-yl>flavan 
• 78306-08-8 (2R,3S,4S)-2,3-trans-3,4-trans-3,3',4',7-tetrahydroxy-4-<(2R,3R)-2,3-cis-3,3',4',5,7-pentahydroxyflavan-8-yl>flavan 
• 97775-91-2 Camelliatannin B 
• 97775-90-1 Camelliatannin A 
• 88269-45-8 (2S,3R,4R,2'R,3'R)-2,2'-Bis-(3,4-dihydroxy-phenyl)-3,4,3',4'-tetrahydro-2H,2'H-[4,8']bichromenyl-3,7,3',5',7'-pentaol 
• 154-23-4 catechin 
• 154-23-4 (-)-catechin 
• 52484-79-4 catechinic acid 
• 154-23-4 catechin 
• 16198-01-9 (-)-epicatechin pentaacetate 

Relevant articles and documents

Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects.

Purification of polar fractions from cacao liquor extracts gave 17 phenolics including four new compounds. The new compounds were characterized as a C-glycosidic flavan, an O-glycoside of a dimeric and two O-glycosides of trimeric A-linked proanthocyanidins, on the basis of spectroscopic data. Isolated polyphenols showed inhibitory effects on nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation in microsomes and on the autoxidation of linoleic acid. These effects were attributed to the radical-scavenging activity in the peroxidation chain reactions, based on the findings that the cacao polyphenols effectively scavenged the 1,1-diphenyl-2-picrylhydrazyl radical.

Furanolysis with Menthofuran: A New Depolymerization Method for Analyzing Condensed Tannins

An improved analytical depolymerization method for characterizing condensed tannins was developed with menthofuran (3,6-dimethyl-4,5,6,7-tetrahydro-1-benzofuran) as the nucleophilic trapping reagent. Herein, menthofuran was compared with routinely used nucleophiles, phloroglucinol and 2-mercaptoethanol. At 30 °C and in the presence of 0.1 M HCl, menthofuran displayed the outstanding ability to enable the fast and full depolymerization of procyanidin B2 using only a 1:1 molar ratio of both reactants. Under the same conditions, phloroglucinol and 2-mercaptoethanol led to a reaction equilibrium with significantly lower conversion yields. Application to commercial tannin extracts showed that a menthofuran-to-extract weight ratio of 1 gave the same yields of procyanidin constitutive units as 10-fold higher molecular equivalent phloroglucinol and 100-fold 2-mercaptoethanol. Finally, guidelines for implementing the menthofuran depolymerization method are proposed to assess the tannin content and composition of extracts as well as of plant materials without prior extraction.

TWO PROANTHOCYANIDINS FROM THE BARK OF DALBERGIA MONETARIA

Key Word Index - Dalbergia monetaria; Leguminosae-Papilionoideae; proanthocyanidin dimers.Abstract - In a chemical investigation of the bark of Dalbergia moneteria the two new proanthocyanidins (2R,3R,4R)-3,3',4',7-tetrahydroxyflavan-(4β->8)-epicatechin and (2R,3R,4R)-3,4',7-trihydroxyflavan-(4β->8)-epicatechin were isolated.

(-)-Epicatechin 5-O-β-D-xylopyranoside from Brosimopsis acutifolium

In addition to 3,4-dihydroxybenzoic acid and (-)-epicatechin, a new glycoside of the latter has been isolated from the methanolic extract of the stem bark of Brosimopsis acutifolium. Its structure was established to be (- )-epicatechin 5-O-β-D-xylopyranoside on the basis of spectroscopic and chemical methods.

Study on in Vitro Preparation and Taste Properties of N-Ethyl-2-Pyrrolidinone-Substituted Flavan-3-Ols

N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) were prepared by an in vitro model reaction, and the taste thresholds of EPSFs and their dose-over-threshold factors in large-leaf yellow tea (LYT) were investigated. The effects of initial reactant

Proanthocyanidin Tetramers and Pentamers from Cinnamomum verum Bark and Their Dentin Biomodification Bioactivities

To enable the further exploration of structure-activity relationships (SARs) of proanthocyanidins (PACs) with dentin biomodification abilities, Cinnamomum verum was selected for scaled-up purification of mixed A-/B-type, medium-size PAC oligomers. Sequential purification by centrifugal partition chromatography (CPC), Sephadex LH-20, and semiprep HPLC chromatography yielded four underivatized tetrameric (5-8) and two pentameric (9-10) PACs. Their unambiguous structural characterization involved extensive spectral and chemical degradation approaches to show that epicatechin units are connected by plant-specific combinations of doubly linked A- and singly linked B-type interflavanyl bonds. The biomechanical properties (via dynamic mechanical analysis) and physicochemical structure (via infrared spectroscopy) were assessed to evaluate the biomodification potency of PAC-treated collagen in a preclinical dentin model. This study revealed that (4→8) versus (4→6) bonds in PAC interflavan linkages have limited influence on biomechanical outcomes of dentin. By exhibiting a 25-fold increase in the complex modulus of treated dentin compared to control, aesculitannin E (5) was found to be the most potent PAC known to date for enhancing the mechanical properties of dentin in this preclinical model.

Benzophenone Glucosides and B-Type Proanthocyanidin Dimers from Zambian Cassia abbreviata and Their Trypanocidal Activities

Two benzophenone glucosides (1 and 2), five flavan-3-ol dimers (5–9), and 17 known compounds (3, 4, and 10–24) were identified from the bark extract of Cassia abbreviata. The chemical structures display two points of interest. First, as an unusual charact

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.

Biochemical and functional characterization of anthocyanidin reductase (ANR) from Mangifera indica L.

Mango (Mangifera indica L.) is abundant in proanthocyanidins (PAs) that are important for human health and plant response to abiotic stresses. However, the molecular mechanisms involved in PA biosynthesis still need to be elucidated. Anthocyanidin reductase (ANR) catalyzes a key step in PA biosynthesis. In this study, three ANR cDNAs (MiANR1-1,1-2,1-3) were isolated from mango, and expressed in Escherichia coli. In vitro enzyme assay showed MiANR proteins convert cyanidin to their corresponding flavan-3-ols, such as (—)-catechin and (—)-epicatechin. Despite high amino acid similarity, the recombinant ANR proteins exhibited differences in enzyme kinetics and cosubstrate preference. MiANR1-2 and MiANR1-3 have the same optimum pH of 4.0 in citrate buffer, while the optimum pH for MiANR1-1 is pH 3.0 in phosphate buffer. MiANR1-1 does not use either NADPH or NADH as co-substrate while MiANR1-2/1-3 use only NADPH as co-substrate. MiANR1-2 has the highest Km and Vmax for cyanidin, followed by MiANR1-3 and MiANR1-1. The overexpression of MiANRs in ban mutant reconstructed the biosynthetic pathway of PAs in the seed coat. These data demonstrate MiANRs can form the ANR pathway, leading to the formation of two types of isomeric flavan-3-ols and PAs in mango.

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.