501-36-0

Basic information

• Product Name: Resveratrol
• Synonyms: TRANS-3,4,5-TRIHYDROXYSTILBENE;TRANS-3,5,4'-STILBENETRIOL;TRANS-RESVERATROL;TRANS-1,2-(3,4',5-TRIHYDROXYDIPHENYL)ETHYLENE;RESVERATROL;RESVERATROLE;3,4',5'-TRIHYDROXY-TRANS-STILBENE;3,4',5-TRIHYDROXY-TRANS-STILBENE
• CAS NO: 501-36-0
• Molecular Formula: C₁₄H₁₂O₃
• Molecular Weight: 228.24
• EINECS: 1308068-626-2
• Product Categories: Stilbenes (substituted);Miscellaneous;Antioxidant;Biochemistry;Stilbenes;Natural Plant Extract;Beauty;The group of Polydatin;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Caspases/Apoptosis;Health supplements;Plant extracts;Inhibitor;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product;Pyridines
• Mol File: 501-36-0.mol
• Article Data: 123

Chemical Properties

• Melting Point: 253-255°C
• Boiling Point: 449.1 °C at 760 mmHg
• Flash Point: 222.3 °C
• Appearance: Off-white/Powder
• Density: 1.359 g/cm³
• Vapor Pressure: 1.11E-08mmHg at 25°C
• Refractive Index: 1.762
• Storage Temp.: −20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).
• PKA: 9.22±0.10(Predicted)
• Water Solubility: Soluble in water (3 mg/100mL), ethanol (50 mg/mL), DMSO (16 mg/mL), DMF (~65 mg/mL), PBS (pH 7.2) (~100µg/mL), methanol
• Stability: Stable for 2 years as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• Merck: 14,8158
• CAS DataBase Reference: Resveratrol(CAS DataBase Reference)
• NIST Chemistry Reference: Resveratrol(501-36-0)
• EPA Substance Registry System: Resveratrol(501-36-0)

Safety Data

• Hazard Codes: Xi
• Statements: 37/38-41-36/38-36-43-22
• Safety Statements: 26-39-37/39-36/37/39
• WGK Germany: 3
• RTECS: CZ8987000
• Hazardous Substances Data: 501-36-0(Hazardous Substances Data)

Usage

Resveratrol Benefits and ralting biological activities

Much of the research pointing to the benefits have been laboratory or animal-based studies. So far, research on resveratrol's effectiveness in humans has yielded mixed results. Anti-Aging and Anti-Cancer Effects Effects on biotransformation enzymes Inhibition of proliferation and induction of apoptosis Inhibition of tumor invasion and angiogenesis Anti-inflammatory effects Protects Cardiovascular Health Inhibition of vascular cell adhesion molecule (VCAM) expression Inhibition of vascular smooth muscle cell (VSMC) proliferation Stimulation of endolethelial nitric oxide synthase (eNOS) activity Inhibition of platelet activiation and aggregation Helps Protect the Brain and Cognitive/Mental Health Stimulation of neurogenesis and microvessel formation Stimulation of β-amyloid peptide clearance Inhibition of neuroinflammation Reduction of oxidative stress

resveratrol sources plants

Resveratrol is anthraquinone terpenoids. It mainly comes from rhizome extract of polygonum cuspidatum. Polygonum cuspidatum: Shrubby perennial herb, up to 1 meter or more. Rhizome lying underground, wood brown, section significantly. Stems erect and cylindrical, surface glabrous, scattered with most red spots, hollow. Leaves alternate, broadly ovate to nearly circular, long 7-12cm, width 5-9cm, apex mucronate, base rounded or cuneate; petiole 1-1.5cm sheath care quality, brown, early fall. Flowering is from July to September, and fruiting from September to October. Spring and autumn can be excavated, cut and dried. Polygonum cuspidatum is born in the valley, creek or shore.

Resveratrol Extraction

Polygonum cuspidatum is the rhizome of polygonaceae polygonum cuspidatum. Polygonum cuspidatum rhizome contains free anthraquinone and anthraquinone glycosides, whch mainly are emodin ether, rhubarb phenol, anthracene glycosides A and B, etc. It also contains resveratrol glycosides, polydatin, protocatechuic acid, dextrose catechin, tree anthrone-8-glucosidecassia, β-sitosterol glucoside and glucose, rhamnose, ginger candy, amino acids, tannin and copper, iron, manganese, zinc, potassium and potassium salts, etc. Figure 1 is Polygonum cuspidatum plant Resveratrol (Res) is a non-flavonoid polyphenol compound. It is considered as a phytoalexin, which is generated when the plant is attacked by pathogenic, or in the poor environment. It is mainly found in grapes, giant knotweed, peanuts, mulberry, pine, Gnetum, Korea Huaifrom 12 families and 31 genera of 72 species of plants. Extraction of the natural plant: polygonum cuspidatum is used as raw material, extracted, extracted resveratrol crude, and then purified. Crude extraction technologies include organic solvent extraction method, the new method of alkaline extraction and enzymatic extraction method. New methods like microwave-assisted extraction, CO2 supercritical extraction and ultrasonic extraction are also applied. The main purpose of purification is to extract cis-resveratrol and trans-resveratrol and polydatin from raw resveratrol to obtain trans-resveratrol. Common methods of purification are chromatography, silica gel column chromatography, thin-layer chromatography, high performance liquid chromatography and the like. Resveratrol had significant antioxidant activity on animal fats. Sample of 240mg/kg shows the strongest antioxidant activity during the three samples whose concentration of resveratrol is respectively 120 mg/kg, 240mg/kg, 360mg/kg. In antioxidant tests on lard, the antioxidant effect of resveratrol is stronger than polyphenols with same concentration.

Contents determination method

C18 column, mobile phase consisted of acetonitrile and water (volume ratio 30: 70), and UV detection at 30 6nm are used to detect. The results show that if the concentration of resveratrol is in 10~250 μg/mL, concentration and peak area show a good linear relationship (r = 0.9999); the recovery is 925% to 1026%; the lowest detectable concentration is 0.6mg/g. The flow rate can be adjusted to detect the enzymatic conversion of polydatin and resveratrol at the same time.

Pharmacological effects

Resveratrol is not only the chemopreventive agents of neoplastic diseases, but also the chemopreventive agents to reduce platelet aggregation and prevent and treat atherosclerosis, cardiovascular and cerebrovascular disease. In the 1990s, studies of science and technology workers on resveratrol have advanced, and reveal its pharmacological effects. It can inhibit normal platelet aggregation, prevent myocardial cram, cerebral embolism. It has a protective effect on cardiac hypoxia, restore decline of cardiac output which is caused by burn or hemorrhagic shock, and can expand arteries and improve microcirculation. In 1998, United States Al.Mindell listed resveratrol as one of “the 100 most popular and effective anti-aging substance” when he compiled the anti-aging Scripture. Peanut oil, peanut butter and other foods rich in resveratrol will be the new fashion of nutrition and health in the 21st century. Resveratrol is the chemopreventive agents of neoplastic diseases, but also the chemopreventive agents to reduce platelet aggregation and prevent and treat atherosclerosis, cardiovascular and cerebrovascular disease. Resveratrol shows some inhibitory effect on staphylococcus aureus, the card he bacteria, escherichia coli, pseudomonas aeruginosa, and has a stronger inhibitory effect on the orphan virus, herpes simplex virus, and enteroviruses, coxsackie a, b groups.

The synthetic method of resveratrol

Resveratrol is an inhibitor of many oxidative metabolism enzymes of aromatic carcinogens. It is named as the natural chemopreventive agents of cardiovascular and cerebrovascular diseases and cancer. Many studies have shown that resveratrol also has many functions, such as anti-mutagenic activity, protecting cell toxicity induced by the oxidation of lipoprotein, inhibiting tumor cell reproduction, and so on. Human separated resveratrol from the root of veratrum grandiflorum for the first time in 1940. Researchers currently has found resveratrol from at least 21 families and 31 genera of 72 species of plants, such as grape vine genus, vitis snake, legumes arachis, cassia, sophora, polygonum, and so on. Because of the low concentration of resveratrol in the plant and the high extraction cost, using chemical, biological, genetic engineering and other methods to obtain resveratrol has become an indispensable means for its development process. The roadmap to synthesis resveratrol is as follows: 3,5-dihydroxybenzoic acid (3) forms 3,5-dihydroxybenzoic acid methyl ester (4) by esterification reaction. Choose methyl ether as phenolic hydroxyl-protecting groups. (4) reacts with dimethyl sulfate to get 3,5-di-methoxybenzoate (5). (5) generates the corresponding benzene methanol (6) after reduction, and forms 3, 5-dimethoxy benzyl bromide (7) through further bromination. Then diethyl (3,5-dimethoxy benzyl) phosphonate (8) can be get by roman abramovich's reaction. (8) reacts with p-anisaldehyde to form the key intermediate 3,4,5-trimethoxy-trans-stilbene (9) via Wittig-Honer reaction. Finally, methyl can be removed by freshly prepared aluminum triiodide. Then the aimed product resveratrol can be separated by thin layer chromatography.

Solubility

Resveratrol is a kinds of natural antioxidants that presents in grapes, red wine, mulberries, peanuts and polygonum cuspidatum. It is polyphenols. It is soluble in organic solvents but insoluble in water. Its dissolved order in organic solvents is: acetone > ethanol> methanol> ethyl acetate> ether> chloroform.

Possible Side effects

Little is known about the safety of long-term or high dose use of resveratrol. Since resveratrol might act like estrogen, some medical experts recommend that people with hormone-sensitive cancers (condition such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids), pregnant women, and children avoid taking resveratrol. In addition, resveratrol could interact with blood thinners like warfarin, aspirin, and ibuprofen by slow blood clotting, which may increase the risk of bleeding in people with bleeding disorders. According to one study, high-dose resveratrol supplementation was associated with fever, reduced blood cells, and decreased blood pressure. There is some concern that high doses of resveratrol supplements could lead to kidney problems in some people.

Uses

Different sources of media describe the Uses of 501-36-0 differently. You can refer to the following data:
1. Resveratrol can prevent the oxidation of low density lipoprotein, and has the potential effect on preventing cardiovascular disease, cancer, antivirus and immune regulation. Its main role is antioxidant properties. Cardiovascular drugs. It can reduce hematic fat and prevent heart disease. It also has the effect on AIDS. Antioxidants and the activity in anti-inflammatory, antithrombotic, anti-cancer, anti-cancer, anti hyperlipidemia and antibacterial. Anti-aging, regulating blood lipid, cardiovascular protection, anti-hepatitis. Resveratrol is a phytoalexin produced naturally by several plants with anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects.
2. raw material for Tamiflu; Oseltamivir
3. Minor constituent of wine, correlated with serum lipid reduction and inhibition of platelet aggregation. Resveratrol is a specific inhibitor of COX-1, and it also inhibits the hydroperoxidase activity of COX-1. It has been shown to inhibit events associated with tumor initiation, promotion and progression.
4. Resveratrol is a natural antioxidant. It reduces blood viscosity, inhibits platelet aggregation and vasodilation, keeps blood flowing smoothly, and prevents the occurrence and development of cancer. It has the effect of preventing and treating atherosclerosis, coronary heart disease, ischemic heart disease and hyperlipidemia. It has tumor-inhibiting effects. Resveratrol also has estrogen-like effects and can be used to treat breast cancer and other diseases. It slows down aging and prevents cancer. Red grape skins, red wine and grape juice contain high concentrations of resveratrol. Studies have shown that as humans age, the integrity of chromosomes is disrupted. However, resveratrol activates proteins that can repair chromosomes, thus slowing down aging.Resveratrol is effective in preventing aging, in part due to its antioxidant properties, and is recommended for use in pre- or post-sun products. Resveratrol can cross the stratum corneum and be found in the dermis and epidermis. It has been shown to protect dermal collagen and may be effective in enhancing glycosaminoglycans, thereby improving tissue hydration. It has been shown to stimulate cell renewal in the skin and to help increase skin thickness. It has been shown to inhibit tyrosinase, which suggests it may be used to reduce hyperpigmentation.

Chemical Properties

Off-White to Tan Powder

Definition

ChEBI:Resveratrol is a stilbenol that is stilbene in which the phenyl groups are substituted at positions 3, 5, and 4' by hydroxy groups. It has a role as a phytoalexin, an antioxidant, a glioma-associated oncogene inhibitor and a geroprotector. It is a stilbenol, a polyphenol and a member of resorcinols.

Synthesis Reference(s)

Tetrahedron Letters, 43, p. 597, 2002 DOI: 10.1016/S0040-4039(01)02227-4

Description

Resveratrol, a non-flavonoid polyphenolic compound, is widely found in the skin of red grapes, nuts, berries, Polygonum cuspidatum root, etc. It is reportedly known to exhibit pharmacological properties including anti-cancer, anti-inflammatory, antioxidant, neuroprotectant, anti-atherogenic property and reduces the synthesis of pro-atherosclerotic substances.

Biological Activity

A phytoestrogen with antitumor, antioxidant, antiplatelet, anti-inflammatory and antifungal effects. Inhibits cytochrome P450 1A1 (IC 50 = 23 μ M) and displays mixed agonist/antagonist actions at ER α and ER β estrogen receptors. Converted into the anticancer agent piceatannol (4-[(1E)-2-(3,5-Dihydroxyphenyl)ethenyl]-1,2-benzenediol ) by cytochrome P450 1B1

Biochem/physiol Actions

ED50 = 15 μM against COX-1

Mechanism of action

Resveratrol can be found in the skins and seeds of grapes and in peanuts. It has demonstrated potent antioxidant, anti-inflammatory, and anti-proliferative activities. Topical application of resveratrol in mice demonstrated photoprotection by significantly decreasing UVB-mediated generation of hydrogen peroxide and infiltration of leukocytes. Its antiproliferative properties are related to the inhibition of cellular events associated with tumor initiation, promotion, and progression, and the triggering of apoptosis in tumor cells.

Anticancer Research

Resveratrol is a stilbinoid, found in the skin of grapes, peanuts, berries, and otherfruits. The cytotoxic effect of resveratrol is mediated via the inhibition of severaltranscription factors; upregulation of caspases, Bax, and p53; and downregulationof survivin, cyclins, and Bcl-2. Increase in Bax/Bcl-2 ratio and upregulation ofcaspases lead to apoptosis. The beneficial effects of resveratrol against cancer havebeen shown in all the stages of cancer including carcinogenesis, initiation,promotion, and progression. It could inhibit Wnt target gene expression in normalcolonic mucosa of the colorectal cancer patients. It increases the caspase-3 inmalignant hepatic tissue and induces anticarcinogenic effects in humangastrointestinal tract (Hosseini and Ghorbani 2015). It has the ability to inhibit thedevelopment of DMBA-induced phenoblastic lesions in the mammary gland organculture (MMOC) model of carcinogenesis and in two-stage full-term mouse model(Balunas and Kinghorn 2005). It prevents carcinogenesis by upregulating Bax andp53 proteins and downregulating NF-κB, COX-2, AP-1, cyclin-dependent kinases,hypoxia-induced factor 1α (HIF-1α), cyclins, MMPs, cytokines, and Bcl-2 proteins(Singh et al. 2016b). It plays a pivotal role in preventing the initiation, promotion,and progression of cancer by inducing phase II drug metabolizing enzymes, bymediating anti-inflammatory effects and inhibiting COX and hydroperoxidasefunctions, and by inducing cell differentiation, respectively, in human promyelocyticleukemic cells (Jang et al. 1997; Aggarwal et al. 2004).Resveratrol, a noteworthy polyphenol occurring in different plants such as grapesand peanuts, has appeared to be required in cell reinforcement, anti-proliferative,anti-inflammatory, and chemopreventive activities. Various potential medicaladvantages, including decreased danger of malignancy and coronary illness, arebelieved to be related to the utilization of resveratrol. It can successfully and proficientlyrepress endothelial cell multiplication and migration, with little cell toxicityin the HUVEC and ARPE19 lines (Cao et al. 2010). Also, there have been perceptionsof inhibitory consequences for smooth muscle cell migration (Venkatesanet al. 2009) and tumor necrosis factor-alpha-incited monocyte adhesion and migration(Kim et al. 2007). As of late, it was recognized that the restraint of PDGF-BB-actuatedcell migration by resveratrol and the particular inhibitors PDGF-R, PI3K,MEK, or p38 in wound healing test agreed with diminished enactment of PDGFBB-incited PDGFR-β, PI3K/Akt, ERK, and p38 phosphory-lation in Western blotinvestigation, recommending that resveratrol hinders cell migration through theinhibition of PI3K/Akt, PDGFR-β, and MAPK cascade (Chan et al. 2013).

References

1) Fremont (2000), Biological effects of resveratrol ; Life Sci., 66 663 2) Howitz et al. (2003), Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan; Nature, 425 191 3) Park et al. (2012), Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases; Cell, 148 421

InChI:InChI=1/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+

Synthetic route

3,5,4'-trimethoxy-trans-stilbene (22255-22-7) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With boron tribromide In dichloromethane at 0 - 30℃;	100%
With boron tribromide In dichloromethane at 0 - 20℃;	99%
With aluminum (III) chloride; sodium sulfate; triethylamine In chlorobenzene at 0 - 115℃; for 6.5h; Inert atmosphere;	98%

(E)-1-(4-(benzyloxy)phenyl)-2-(3,5-bis(benzyloxy)phenyl)-ethene (89946-06-5) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
Stage #1: (E)-1-(4-(benzyloxy)phenyl)-2-(3,5-bis(benzyloxy)phenyl)-ethene With aluminum (III) chloride; triethylamine In chlorobenzene at 0 - 80℃; for 10h; Stage #2: With water In chlorobenzene at 0℃; for 2h; Product distribution / selectivity;	100%
With aluminum (III) chloride; N,N-dimethyl-aniline at 40 - 50℃;	90%
With hydrogen In dichloromethane at 20℃; under 3750.38 Torr; for 5h;	87%

(E)-3,5,4'-tri(benzoyloxy)styrene (710969-83-8) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With sodium methylate In tetrahydrofuran; methanol at 50℃; for 5h;	98%

(E)-4-(3,5-bis(methoxymethoxy)styryl)phenol (1217011-33-0) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With hydrogenchloride In methanol; water at 20 - 65℃; for 3h; Inert atmosphere;	97%

3,5-dihydroxybenzaldehyde (26153-38-8) + dimethyl (4-hydroxybenzyl)phosphonate (68997-88-6) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With RS004 catalyst In ethanol at 20℃; for 6h; Wittig-Horner Reaction;	97%

4'-Acetylresveratrol (411233-11-9) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran for 2h; Heating;	95%

3,5,4'-trimethoxystilbene (22255-22-7, 94608-23-8, 63844-75-7) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
Stage #1: 3,5,4'-trimethoxystilbene With boron tribromide In toluene at 0 - 20℃; for 2.03333h; Stage #2: With water; sodium hydrogencarbonate In toluene at 0℃; for 0.333333h;	92%
With aluminum (III) chloride; triethylamine In chlorobenzene at 60 - 70℃; for 0.5h; Inert atmosphere;	90%
Multi-step reaction with 2 steps 1: BBr3 2: diphenyl disulphide / tetrahydrofuran / Heating View Scheme
With pyridine hydrochloride at 190 - 195℃; for 4h;
Stage #1: 3,5,4'-trimethoxystilbene With iodine In hexane for 48h; Reflux; Stage #2: With boron tribromide In dichloromethane at 0 - 20℃; for 5h;

(E)-2,4,6-tribromo-3,5,4'-trihydroxystilbene (1399502-89-6) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With sodium sulfite In water at 60℃; for 6h; Green chemistry;	90%

triacetyl-trans-resveratrol (42206-94-0) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran	88%
Stage #1: triacetyl-trans-resveratrol With potassium hydroxide In methanol for 1h; Inert atmosphere; Reflux; Stage #2: With hydrogenchloride In methanol; water pH=2; Inert atmosphere;	79%
With sodium methylate In tetrahydrofuran; methanol
With potassium hydroxide In methanol; ethyl acetate

(E)-1-(3,5-di-isopropoxyphenyl)-2-(4-isopropoxyphenyl)ethene (587870-67-5) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With boron trichloride In dichloromethane at -78 - -10℃;	85%

C15H12O5(C2H2O)3 → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With 1-methyl-1H-imidazole; sodium hydrogencarbonate for 0.333333h; Heating; microwave irradiation;	84%

(Z)-1-(3,5-dimethoxyphenyl)-2-(4-methoxyphenyl)ethene (94608-23-8) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With aluminium(III) iodide In acetonitrile at 82℃; for 3h;	83.8%
With aluminium(III) iodide In acetonitrile at 82℃; for 3h;	73%

pinosylvin (22139-77-1) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With L234Q/I238V/G239A In dimethyl sulfoxide at 20℃; for 20h; Reagent/catalyst; Enzymatic reaction; regioselective reaction;	83%
With unspecific peroxygenase from Marasmius rotula DSM-25031; dihydrogen peroxide; ascorbic acid In aq. phosphate buffer; acetone at 30℃; for 0.5h; pH=7; Enzymatic reaction; regioselective reaction;

C15H12O5 (906463-95-4) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline at 180 - 190℃; Microwave irradiation; Inert atmosphere; Green chemistry;	82%

5-[(1E)-2-(phenylbenzyloxy)vinyl]-1,3-cyclohexanedione → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In acetonitrile under 2280.15 Torr; for 48h;	80%

(E)-1-(3,5-bis-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)ethene (676596-85-3) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With hydrogenchloride In ethanol at 20℃; for 26h;	79%
With hydrogenchloride In methanol at 20℃; for 36h;

1-(1-bromoethyl)-3,5-diacetoxybenzene (1026420-83-6) + 4-bromophenyl acetate (1927-95-3) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
Stage #1: 1-(1-bromoethyl)-3,5-diacetoxybenzene With lithium carbonate In ISOPROPYLAMIDE at 120℃; for 2h; Inert atmosphere; Stage #2: 4-bromophenyl acetate With potassium phosphate; palladium oximate In ISOPROPYLAMIDE at 130℃; for 19.75h; Inert atmosphere; Stage #3: With water; potassium carbonate at 110℃; for 2.5h; Product distribution / selectivity;	77%

4-hydroxy-benzaldehyde (123-08-0) + (3,5-dihydroxybenzyl)triphenylphosphonium bromide → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 80℃;	75%

(E)-1-[4-(hexyloxy)phenyl]-2-(3,5-dimethoxyphenyl)ethene (190371-53-0) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With boron tribromide In dichloromethane at 0 - 20℃; for 4h;	70%

(E)-2-(4'-hydroxyphenyl)-3-(3',5'-dihydroxyphenyl)acrylic acid → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With quinoline; copper at 200℃; for 3h; Inert atmosphere; diastereoselective reaction;	60.8%
With quinoline; copper

2-(3,5-dihydroxyphenyl)acetic acid (4670-09-1) + 4-hydroxy-benzaldehyde (123-08-0) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With piperidine; 1-methyl-1H-imidazole In various solvent(s) at 160℃; for 0.166667h; microwave irradiation;	51%

5-iodoresorcinol (64339-43-1) + 4-Vinylphenol (2628-17-3) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With triethanolamine; palladium diacetate at 100℃; for 24h; Mizoroki-Heck reaction; Inert atmosphere;	41.4%
With triethanolamine; palladium diacetate at 100℃; for 24h; Mizoroki-Heck reaction; Inert atmosphere; stereoselective reaction;	41.4%
With triethanolamine; palladium diacetate at 100℃; for 24h; Heck Reaction; Inert atmosphere;

5-[(E)-2-(4-methoxyphenyl)vinyl]benzene-1,3-diol (65728-21-4, 33626-08-3) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With pyridine hydrochloride
With boron trichloride; tetra-(n-butyl)ammonium iodide In dichloromethane at 0℃; for 7h; Inert atmosphere;	81 mg

polydatin (27208-80-6, 65914-17-2, 148766-36-3) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
In water at 21℃; for 14h; β-glucosidase, pH 6;
With proteolytic enzymes at 0 - 15℃; Enzymatic reaction;
With recombinant β-glucosidase from Thermotoga maritima In aq. phosphate buffer; dimethyl sulfoxide at 90℃; pH=5.8; Kinetics; Enzymatic reaction;
With glucosidases from Bacillus safensis CGMCC 13129 at 37℃; for 8h; pH=7; Temperature; pH-value; Enzymatic reaction;

resveratrol (501-36-0, 61434-67-1, 133294-37-8) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With diphenyldisulfane In tetrahydrofuran Isomerization; Heating;

2-<4-hydroxy-phenyl>-3-<3,5-dihydroxy-phenyl>-acrylic acid → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With quinoline; copper at 220℃;

3,5,4'-triacetoxy-trans(?)-stilbene → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0)

Conditions	Yield
With sodium hydroxide
With sodium hydroxide

cis-3,4',5-triisopropoxystilbene (587870-59-5) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + cis-resveratrol (61434-67-1)

Conditions	Yield
With boron trichloride In dichloromethane at -78 - 0℃; for 2.25h;

4-Vinylphenol (2628-17-3) + 1,3-dihydroxy-5-vinylbenzene (113231-14-4) → (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + (E)-3,3',5,5'-tetrahydroxystilbene (33626-09-4)

Conditions	Yield
Grubbs catalyst first generation In tetrahydrofuran for 1h; Heating;	A 95 % Chromat. B 5 % Chromat.

diazomethane (186581-53-3, 908094-01-9) + (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → 3,5,4'-trimethoxy-trans-stilbene (22255-22-7)

Conditions	Yield
In methanol; diethyl ether at 10℃; for 24h;	100%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + acetic anhydride (108-24-7) → triacetyl-trans-resveratrol (42206-94-0)

Conditions	Yield
With pyridine at 20 - 80℃;	100%
With sodium hydroxide In dichloromethane; water at 20℃; Concentration; Reagent/catalyst; Solvent; Temperature; Large scale;	95%
With triethylamine In dichloromethane at 20℃;	92%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + methyl iodide (74-88-4) → 3,5,4'-trimethoxy-trans-stilbene (22255-22-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h;	100%
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With potassium carbonate In acetone at 25℃; for 0.0833333h; Inert atmosphere; Stage #2: methyl iodide In acetone at 25℃; for 12h; Inert atmosphere;	93%
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With potassium carbonate In acetone at 25℃; for 0.0833333h; Inert atmosphere; Stage #2: methyl iodide In acetone at 25℃; for 12h; Inert atmosphere;	93%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-a-D-galactopyranoside (3068-32-4) → resveratrol galactoside conjugate peracetate

Conditions	Yield
With 2,4,6-trimethyl-pyridine; silver carbonate; molecular sieve, 3 A In dichloromethane; acetonitrile at 25℃; for 72h; Under anhydrous N2;	100%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → (E)-3,5,4'-trihydroxy-2,4,6-trideuterostilbene

Conditions	Yield
With perchloric acid; deuteromethanol at 20℃; for 4h; Reagent/catalyst; Inert atmosphere;	100%
With water-d2 In acetonitrile at 90℃; for 24h; Darkness;

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → trans-piceatannol (10083-24-6)

Conditions	Yield
With streptomyces avermilitis tyrosinase; benzene-1,2-diol In aq. buffer for 3h; pH=8; Reagent/catalyst; Enzymatic reaction;	100%
With ascorbic acid In aq. phosphate buffer; dimethyl sulfoxide at 30℃; pH=6.0;	100%
With benzene-1,2-diol In aq. phosphate buffer at 30℃; pH=7.5; Microbiological reaction; regioselective reaction;

trifluoromethylsulfonic anhydride (358-23-6) + (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → C17H9F9O9S3

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃;	100%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + piperidine carbamoyl chloride (13939-69-0) → (E)-3,5,4'-tri[(piperidine-N-carbonyl)oxy]stilbene (1416356-15-4)

Conditions	Yield
With dmap; potassium carbonate In acetone Reflux; Inert atmosphere;	99.3%

4-Nitrophthalonitrile (31643-49-9) + (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → C38H18N6O3

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 80℃; Inert atmosphere;	99%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + n-hexadecanoyl chloride (112-67-4) → resveratrol tripalmitate (411233-17-5)

Conditions	Yield
With pyridine at 20℃; for 12h;	99%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + carbonochloridic acid, butyl ester (592-34-7) → resveratrol tris(butyl carbonate)

Conditions	Yield
With pyridine In toluene at 20℃;	99%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → dihydroresveratrol (58436-28-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal	98%
With 5%-palladium/activated carbon; hydrogen In methanol at 20℃; under 2250.23 Torr; for 3h;	97.82%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; under 3800.26 Torr; for 8h;	95%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + n-octanoic acid chloride (111-64-8) → [4-[(E)-2-[3,5-di(octanoyloxy)phenyl]vinyl]phenyl] octanoate

Conditions	Yield
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With dmap; triethylamine In dichloromethane at 10℃; Stage #2: n-octanoic acid chloride In dichloromethane at 10℃; for 1h;	96.7%
With potassium carbonate In acetonitrile at 25℃; for 20h;	20%
With pyridine
With pyridine at 20℃;
With potassium carbonate In acetonitrile at 25℃; for 20h;

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → (E)-2,4-dihydroxyl-6-(4′-hydroxylstyryl)benzaldehyde

Conditions	Yield
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol; N,N-dimethyl-formamide With trichlorophosphate In acetonitrile at 20℃; for 2.5h; Vilsmeier reaction; Cooling with ice; Stage #2: With water In acetonitrile at 50℃; for 3h; Vilsmeier reaction;	96%
With trichlorophosphate In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2.5h; Vilsmeier Reaction; Cooling with ice;	96%
With trichlorophosphate at 20℃; for 3h; Cooling with ice;	95%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + acetic anhydride (108-24-7) → acetyl-trans-resveratrol

Conditions	Yield
With triethylamine In ethyl acetate at 0 - 70℃; for 2h;	96%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + benzyl bromide (100-39-0) → (E)-1-(4-(benzyloxy)phenyl)-2-(3,5-bis(benzyloxy)phenyl)-ethene (89946-06-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	95%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + potassium hydrogencarbonate (298-14-6) → (E)-2,6-dihydroxy-4-(4-hydroxystyryl)benzoic acid

Conditions	Yield
With Lyophilized E. coli whole cells overexpressed Rhizobium sp. 2,6-dihydroxybenzoic acid decarboxylase In methanol; aq. phosphate buffer at 30℃; for 24h; pH=8.5; Catalytic behavior; Reagent/catalyst; Solvent; Enzymatic reaction; regioselective reaction;	95%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) + 2-ethylhexanoic acid chloride (760-67-8) → (E)-5-(4-(2-ethylhexanoyloxy)styryl)-1,3-phenylene bis(2-ethylhexanoate)

Conditions	Yield
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With dmap; triethylamine In dichloromethane at 10℃; Stage #2: 2-ethylhexanoic acid chloride In dichloromethane at 10℃; for 1h;	94.8%

3,3-Dimethylacryloyl chloride (3350-78-5) + (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → (E)-5-(4-(3-methylbut-2-enoyloxy)styryl)-1,3-phenylene bis(3-methylbut-2-enoate)

Conditions	Yield
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With dmap; triethylamine In dichloromethane at 10℃; Stage #2: 3,3-Dimethylacryloyl chloride In dichloromethane at 10℃; for 1h;	92.5%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → trans-δ-viniferin (62218-12-6)

Conditions	Yield
With dihydrogen peroxide In water; acetone at 40℃; for 1h; Reagent/catalyst;	92%
Stage #1: (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol With horseradish peroxidase In acetone at 40℃; for 0.5h; pH=8; Stage #2: With dihydrogen peroxide In acetone at 40℃; for 1h; pH=8;	89%
With silver(I) acetate In methanol at 50℃; for 1h;	86%

(E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → cis-resveratrol (61434-67-1)

Conditions	Yield
for 1.66667h; Irradiation; isomerization;	90.6%
Inert atmosphere; UV-irradiation;	81%
In ethanol Irradiation;

imidazol-1-ylacetic acid (22884-10-2) + (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol (501-36-0) → (E)-3-hydroxy-5-(4-hydroxystyryl)phenyl 2-(1H-imidazol-1-yl)acetate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 60℃; for 3h;	90%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 60℃; for 3h;	90%

Upstream product

• 22255-22-7 3,5,4'-trimethoxystilbene 
• 18259-15-9 3,5-dimethoxy-4'-hydroxystilbene 
• 22255-22-7 3,5,4'-trimethoxy-trans-stilbene 
• 190371-53-0 (E)-1-[4-(hexyloxy)phenyl]-2-(3,5-dimethoxyphenyl)ethene 
• 501-36-0 resveratrol 
• 2628-17-3 4-Vinylphenol 
• 113231-14-4 1,3-dihydroxy-5-vinylbenzene 
• 877-88-3 3,5-dimethoxybenzyl bromide 
• 24131-30-4 (3,5-dimethoxybenzyl)triphenylphosphonium bromide 
• 123-11-5 4-methoxy-benzaldehyde 
• 58605-10-0 methyl 3,5-bis(benzyloxy)benzoate 
• 2628-16-2 p-acetoxystyrene 
• 22139-77-1 pinosylvin 
• 27208-80-6 polydatin 

Downstream Products

• 22255-22-7 3,5,4'-trimethoxy-trans-stilbene 
• 42206-94-0 triacetyl-trans-resveratrol 
• 62218-12-6 trans-δ-viniferin 
• 108-95-2 phenol 
• 625096-18-6 (+)-davidiol A 
• 123-08-0 4-hydroxy-benzaldehyde 
• 3011-34-5 4-hydroxy-3-nitrobenzaldehyde 
• 1001421-74-4 1,3-BIS-nitrooxy-5-[2-(4-nitrooxy-phenyl)-vinyl)-benzene 
• 4359-97-1 2,6-di-tert-butyl-4-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-cyclohexa-2,5-dienone 
• 637776-90-0 3,4'-dibenzyloxyresveratrol 
• 38963-95-0 trans-resveratroloside 
• 27208-80-6 polydatin 

Relevant articles and documents

Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells

Resveratrol is a naturally occurring defense compound produced by a limited number of plants in response to stresses. Besides cardiovascular benefits, this health-promoting compound has been reported to extend life spans in yeasts, flies, worms, and fish. To biosynthesize resveratrol de novo, tyrosine ammonia lyase (TAL), 4-coumarate CoA-ligase (4CL), and stilbene synthase (STS) were isolated from Rhodobacter sphaeroides, Arabidopsis thaliana, and Vitis vinifera, respectively. Yeast cells expressing 4CL and STS produce resveratrol when fed with 4-coumaric acid, the substrate of 4CL. When a translational fusion protein joining 4CL and STS was used, yeast cells produced 15-fold more resveratrol than the cotransformed cells, suggesting that physical localization of 4CL and STS facilitate resveratrol production. When the resveratrol pathway was introduced into human HEK293 cells, de novo biosynthesis was detected, leading to intracellular accumulation of resveratrol. We successfully engineered an entire plant natural product pathway into a mammalian host. Copyright

An innovative biotransformation to produce resveratrol by: Bacillus safensis

Resveratrol is considered as a potential food supplement, cosmetic ingredient and nutraceutical. In this study, resveratrol was produced by biotransformation successfully. In detail, a β-glucosidase producing strain was isolated and identified as Bacillus safensis, and it could convert polydatin to resveratrol efficiently and rapidly. Further research showed that the conversion rate to resveratrol reached 93.1% in 8 h at 37 °C. The production of resveratrol was confirmed by HPLC, LC-MS and 1H-NMR to identify its structure and it was verified to possess antibacterial properties especially against Escherchia coli. To illustrate the resveratrol transformation mechanism, several glucosidases from B. safensis CGMCC 13129 were expressed and analyzed. The results showed that BGL4 and BGL5 had higher transformation activity compared with other tested glucosidases. This research provides a novel approach to produce resveratrol, and would promote the application of resveratrol in health-promoting pharmaceutical and food products.

Identification of metabolic pattern and bioactive form of resveratrol in human medulloblastoma cells

Cancer preventive reagent trans-resveratrol is intracellularly biotransformed to different metabolites. However, it is still unclear whether trans-resveratrol exerts its biological effects directly or through its metabolite(s). This issue was addressed here by identifying the metabolic pattern and the bioactive form of resveratrol in a resveratrol-sensitive human medulloblastoma cell line, UW228-3. The cell lysates and condition media of UW228-3 cells with or without 100 μM resveratrol treatment were analyzed by HPLC and LC/MS which revealed (1) that resveratrol was chemically unstable and the spontaneous generation of cis-resveratrol reduced resveratrol's anti-medulloblastoma efficacy and (2) that resveratrol monosulfate was the major metabolite of the cells. To identify the bioactive form of resveratrol, a mixture-containing approximately half fraction of resveratrol monosulfate was prepared by incubating trans-resveratrol with freshly prepared rat brain lysates. Medulloblastoma cells treated by 100 μM of this mixture showed attenuated cell crisis. The overall levels of the three brain-associated sulfotransferases (SULT1A1, 1C2 and 4A1) were low in medulloblastoma cells in vivo and in vitro in comparison with that in human noncancerous and rat normal cerebella; resveratrol could more or less up-regulate the production of these enzymes in UW228-3 cells but their overall level was still lower than that in normal cerebellum tissue. Our study thus demonstrated for the first time that trans-resveratrol is the bioactive form in medulloblastoma cells in which the expression of brain-associated SULTs was down-regulated, resulting in the increased intracellular bioavailability and anti-medulloblastoma efficacy of trans-resveratrol.

Tandem Acceptorless Dehydrogenative Coupling-Decyanation under Nickel Catalysis

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A Simple Nickel Catalyst Enabling an E-Selective Alkyne Semihydrogenation

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