36062-04-1

Basic information

• Product Name: SabiWhite-
• Synonyms: SabiWhite-;3,5-Heptanedione, 1,7-bis(4-hydroxy-3-methoxyphenyl)-;1,7-bis(4-hydroxy-3-methoxy-phenyl)heptane-3,5-dione;Tetrahydrocurcumin;TETRAHYDROCURCUMINOID;Tetrahydrodiferuloylmethane;Aids110028;Aids-110028
• CAS NO: 36062-04-1
• Molecular Formula: C₂₁H₂₄O₆
• Molecular Weight: 372.415
• EINECS: 1592732-453-0
• Product Categories: Aromatics;Inhibitors;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 36062-04-1.mol

Chemical Properties

• Melting Point: 95-97 ºC
• Boiling Point: 564.1 °C at 760 mmHg
• Flash Point: 196℃
• Appearance: /
• Density: 1.222
• Storage Temp.: -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 9.12±0.10(Predicted)
• Stability: Light Sensitive
• BRN: 3485469
• CAS DataBase Reference: SabiWhite-(CAS DataBase Reference)
• NIST Chemistry Reference: SabiWhite-(36062-04-1)
• EPA Substance Registry System: SabiWhite-(36062-04-1)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 36062-04-1(Hazardous Substances Data)

Usage

Uses

Used in Skincare Industry:
SabiWhiteis used as an antioxidant and skin-whitening ingredient for its protective effects against oxidative stress and its ability to depigment the skin.
Used in Pharmaceutical Industry:
SabiWhiteis used as a neuroprotective agent for its potential therapeutic effects in improving mitochondrial dysfunction in the ischemic stroke mice model and its potential in treating cancer and dementia.
Used in Antioxidant Applications:
SabiWhiteis used as an antioxidant for its potent antioxidant activity, which helps protect against diabetes and vascular dysfunction by alleviating oxidative stress.
Used in Solvent Applications:
SabiWhiteis used as a soluble compound in various organic solvents such as methanol, ethanol, and DMSO, making it suitable for use in a range of applications where solubility is required.

Preparation

Tetrahydrocurcumin can also be chemically synthesized from curcumin by catalytic hydrogenation using PtO2 or palladium as a catalyst.One gram (1.0 g) of curcumin was dissolved in 20 ml of acetone and placed in a 100-ml glass reactor for reduction, to which was then added 500 mg of activated Raney-nickel catalyst. Subsequently, the atmosphere of the reactor was replaced for hydrogen gas by the routine method. A rubber-made balloon filled with hydrogen gas was arranged on the upper portion of the reactor in order to keep hydrogen gas pressure constant in the reactor by supplying hydrogen gas to make up for the consumed amount of hydrogen gas. The reactor was stirred while maintained at a given temperature in a constant-temperature water bath kept at 30° C. for 2-hour reduction.After completion of the reaction, the Raney-nickel catalyst was removed from the solution by filtering, which was then evaporated and dried by concentration under reduced pressure and was dissolved again in a small amount of acetone.Subsequently, the eluate was concentrated and dried under reduced pressure to obtain 674 mg of tetrahydrocurcumin.Method for making tetrahydrocurcumin and a substance containing the antioxidative substance tetrahydrocurcumin

benefits

Tetrahydrocurcumin (ultra pure whitening element) is a natural functional whitening ingredient extracted from the roots of Ginger Curcuma longa. It has strong activity of inhibiting tyrosinase. The whitening effect is better than that of arbutin. It can effectively inhibit the generation of oxygen free radicals and remove the formed free radicals. It has obvious antioxidant, inhibits melanin, repairs freckle, anti-inflammatory activity, blocks the inflammatory process, etc. In addition, tetrahydrocurcumin has potent antioxidant activity and potential anti-aging benefits.

Biological Activity

Tetrahydrocurcumin is a metabolite of curcumin that has diverse biological activities, including antioxidant, anti-inflammatory, anti-angiogenic, and anticancer properties. It scavenges 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals in a cell-free assay with an EC50 value of 16.8 μM. Tetrahydrocurcumin (50 μM) inhibits LPS-induced increases in inducible nitric oxide synthase (iNOS) and COX-2 expression in RAW 264.7 cells. It also inhibits LPS-induced increases in TNF-α release when used at a concentration of 100 μM and increases in nitric oxide (NO) production and IL-6 levels in a concentration-dependent manner. Tetrahydrocurcumin reduces carrageenan-induced paw edema in rats (ED50 = 20 mg/kg). It also reduces the formation of neocapillaries and decreases microvascular density as well as VEGF, VEGF receptor 2 (VEGFR2), and hypoxia-inducible factor-1α (HIF-1α) expression in a CaSki cervical cancer nude mouse xenograft model when administered at doses of 100, 300, and 500 mg/kg.

InChI:InChI=1/C21H24O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h5-6,9-12,24-25H,3-4,7-8,13H2,1-2H3

Synthetic route

1,7-bis(4’-acetoxy-3’-methoxyphenyl)-3,5-heptadione (52199-86-7) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With water; sodium carbonate; sodium hydroxide In methanol; ethanol at 100℃; for 1h; Temperature; Reagent/catalyst; Solvent;	95%

curcumin (458-37-7) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With platinum-iron-nickel hydroxide composite nanoparticle catalyst In ethanol at 24℃; for 1h;	92.9%
With palladium on activated charcoal; hydrogen In ethanol under 103.432 Torr; for 4h;	91.8%
With hydrogen; palladium on activated charcoal In ethyl acetate at 20℃; for 2h;	80%

curcumin (458-37-7, 94875-80-6) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With 1,4-dihydropyridine; palladium on activated charcoal In ethanol for 8h; Reflux;	86%
With NADPH-dependent curcumin/dihydrocurcumin reductase from Escherichia coli DH10B; NADPH at 28℃; for 0.5h; Enzymatic reaction;
With platinum(IV) oxide

curcumin (458-37-7) → hexahydrocurcumin (36062-05-2, 39886-84-5, 93559-28-5, 100667-55-8) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With palladium on activated charcoal	A 18% B 68%

curcumin (458-37-7) → hexahydrocurcumin (36062-05-2, 39886-84-5, 93559-28-5, 100667-55-8) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 1,7-bis-(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (36062-07-4, 112494-41-4, 135413-63-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; under 760.051 Torr; for 4h;	A 20% B 64% C 15%
With 5% palladium on activated carbon; hydrogen In ethanol

curcumin (98885-93-9, 115851-80-4, 147556-16-9) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal In chloroform; ethyl acetate at 100℃; under 38000 Torr;	60.5%

curcumin (98885-93-9, 115851-80-4, 147556-16-9) → hexahydrocurcumin (36062-05-2, 39886-84-5, 93559-28-5, 100667-55-8) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 1,7-bis-(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (36062-07-4, 112494-41-4, 135413-63-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol at 20℃; under 760 Torr; for 4h;	A 9% B 14% C 5%
With hydrogen; palladium on activated charcoal In methanol for 20h; Ambient temperature;	A 0.6 g B 1.8 g C 2.4 g
With hydrogen; palladium on activated charcoal In ethyl acetate under 2327.17 Torr;

vanillin (121-33-5) + 5-fluoro-2-trifluoromethylbenzyl halide → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: B2O3; B(OC4H9)3; n-BuNH2 / ethyl acetate 2: H2 / Pd-C / ethyl acetate View Scheme

acetylacetone (123-54-6) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: B2O3; B(OC4H9)3; n-BuNH2 / ethyl acetate 2: H2 / Pd-C / ethyl acetate View Scheme

glucose (115945-70-5) + curcumin (458-37-7) → 4,4'-di-O-(β-D-glucopyranosyl)curcumin + curcumin 4'-O-β-D-glucoside (387818-26-0) + dihydrocurcumin-O-glucoside (1352455-17-4) + octahydrocurcumin-O-glucoside (1352455-15-2) + hexahydrocurcumin-O-glucoside + hexahydrocurcumin (36062-05-2, 39886-84-5, 93559-28-5, 100667-55-8) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 1,7-bis-(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (36062-07-4, 112494-41-4, 135413-63-7) + (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-ene-3,5-dione + (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-diol

Conditions	Yield
With Rhizopus chinensis IFFI 3043 at 25℃; for 24h; Microbiological reaction;

...Expand

curcumin (458-37-7, 94875-80-6) → dihydrocurcumin (917909-26-3) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
With NADPH-dependent curcumin/dihydrocurcumin reductase from Escherichia coli DH10B; NADPH at 28℃; Kinetics; Concentration; Time; Enzymatic reaction;

curcumin (458-37-7) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-ene-3,5-dione

Conditions	Yield
With recombinant Vibrio vulnificus curcumin reductase; NADPH In aq. phosphate buffer; ethanol at 35℃; pH=6; Kinetics; Enzymatic reaction;

(E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid (1135-24-6) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 5%-palladium/activated carbon; hydrogen / dichloromethane; methanol / 16 h / 2585.81 Torr 2.1: sodium hydroxide / water / 16 h / 20 °C / Cooling 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 4.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 4.2: 18 h / 20 °C 5.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 5.2: 3 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: 5%-palladium/activated carbon; hydrogen / dichloromethane; methanol / 16 h / 2585.81 Torr 2.1: sodium hydroxide / water / 16 h / 20 °C / Cooling 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 4.1: triethylamine; magnesium chloride / acetonitrile / 1 h / 0 °C 4.2: 18 h / 20 °C 5.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 5.2: 18 h / 20 °C 6.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 6.2: 3 h / 20 °C View Scheme

3-(4-hydroxy-3-methoxyphenyl)propionic acid (1135-23-5) → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water / 16 h / 20 °C / Cooling 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 3.2: 18 h / 20 °C 4.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 4.2: 3 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: sodium hydroxide / water / 16 h / 20 °C / Cooling 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 3.1: triethylamine; magnesium chloride / acetonitrile / 1 h / 0 °C 3.2: 18 h / 20 °C 4.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 4.2: 18 h / 20 °C 5.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 5.2: 3 h / 20 °C View Scheme

C17H16O5 → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 2.2: 18 h / 20 °C 3.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 3.2: 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1.17 h / 20 °C 2.1: triethylamine; magnesium chloride / acetonitrile / 1 h / 0 °C 2.2: 18 h / 20 °C 3.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 3.2: 18 h / 20 °C 4.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 4.2: 3 h / 20 °C View Scheme

C17H15ClO4 → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine; magnesium chloride / acetonitrile / 1 h / 0 °C 1.2: 18 h / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 1.17 h / 0 - 20 °C 2.2: 18 h / 20 °C 3.1: sodium chloride; water / dimethyl sulfoxide / 3 h / 150 °C 3.2: 3 h / 20 °C View Scheme

C38H36O10 → 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1)

Conditions	Yield
Stage #1: C38H36O10 With water; sodium chloride In dimethyl sulfoxide at 150℃; for 3h; Stage #2: With sodium methylate In methanol at 20℃; for 3h;	0.44 g

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 1,2-diamino-benzene (95-54-5) → 4,4'-((3H-benzo[b]-[1,4]-diazepine-2,4-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃;	97.5%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 4-Chloro-1,2-phenylenediamine (95-83-0) → 4,4'-((7-chloro-3H-benzo[b]-[1,4]-diazepine-2,4-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃;	96.1%

4,5-Dichloro-1,2-phenylenediamine (5348-42-5) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 4,4’-((7,8-dichloro-3H-benzo[b]-[1,4]-diazepine-2,4-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃;	96.1%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 2-Amino-5-chlorobenzophenone (719-59-5) → 1-(6-chloro-2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one (1408335-44-3)

Conditions	Yield
With trifluoroacetic acid at 100℃; for 0.666667h;	95%

C19H13Cl2NO + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 1-(6-chloro-4-(2-chlorophenyl)-2-(4-hydroxy-3-methoxyphenethyl)quinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one

Conditions	Yield
With trifluoroacetic acid at 100℃; for 1h;	95%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + (2-aminophenyl)(phenyl)methanone (2835-77-0) → 1-(2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one (1408335-42-1)

Conditions	Yield
With trifluoroacetic acid at 100℃; for 0.5h;	93%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 4-Bromo-benzene-1,2-diamine (1575-37-7) → 4,4'-((7-bromo-3H-benzo[b]-[1,4]-diazepine-2,4-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃;	90.7%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 1,7-bis-(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (36062-07-4, 112494-41-4, 135413-63-7)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran at 20℃; for 5h;	89%
With sodium tetrahydroborate In 1,4-dioxane; water at 20℃; for 1h;	73.7%

4-fluoro-1,2-phenylenediamine (367-31-7) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 4,4'-((7-fluoro-3H-benzo[b]-[1,4]-diazepine-2,4-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃;	88.8%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 4-amino-benzoic acid (150-13-0) → C28H28N2O8

Conditions	Yield
Stage #1: 4-amino-benzoic acid With sodium nitrite In water at 3 - 5℃; for 0.25h; Stage #2: With hydrogenchloride In water for 0.0833333h; Stage #3: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione With sodium hydroxide In water at 25℃; for 0.5h; pH=10;	85.1%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + ethylenediamine (107-15-3) → 4,4’-((3,6-dihydro-2H-1,4-diazepine 5,7-diyl)bis(ethane-2,1-diyl))bis-(2-methoxyphenol)

Conditions	Yield
With sulfuric acid In ethanol at 20℃; for 2h;	85%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 2-aminoacetophenone (551-93-9) → 1-(2-(4-hydroxy-3-methoxyphenethyl)-4-methylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one (1408335-41-0)

Conditions	Yield
With trifluoroacetic acid at 100℃; for 0.666667h;	84%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → (Z)-5-amino-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one

Conditions	Yield
With ammonium acetate; toluene-4-sulfonic acid In ethanol for 2h;	80%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + methyl iodide (74-88-4) → 1,7-bis(3,4-dimethoxyphenyl)-4,4-dimethylheptane-3,5-dione (1537182-88-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 72h;	79%

p-Aminohippuric acid (61-78-9) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → C30H31N3O9

Conditions	Yield
Stage #1: p-Aminohippuric acid With sodium nitrite In water at 3 - 5℃; for 0.25h; Stage #2: With hydrogenchloride In water for 0.0833333h; Stage #3: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione With sodium hydroxide In water at 25℃; for 0.5h; pH=10;	78.23%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + benzaldehyde (100-52-7) + urea (57-13-6) → 6-(4-hydroxy-3-methoxyphenethyl)-5-(3-(4-hydroxy-3-methoxyphenyl)propanoyl)-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (1432038-10-2)

Conditions	Yield
Stage #1: benzaldehyde; urea With copper(ll) sulfate pentahydrate In ethanol at 80℃; for 0.25h; Biginelli Pyrimidone Synthesis; Stage #2: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione In ethanol at 80℃; for 24h; Biginelli Pyrimidone Synthesis;	74%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → C21H25NO6

Conditions	Yield
With pyridine; hydroxylamine hydrochloride at 20℃; for 1h;	70%

2,5-diaminobenzophenone (18330-94-4) + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 1-(6-amino-2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one (1408335-45-4)

Conditions	Yield
With trifluoroacetic acid at 100℃; for 1.5h;	70%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 4-nitrobenzaldehdye (555-16-8) + urea (57-13-6) → C29H29N3O8 (1432038-14-6)

Conditions	Yield
Stage #1: 4-nitrobenzaldehdye; urea With copper(ll) sulfate pentahydrate In ethanol at 80℃; for 0.25h; Biginelli Pyrimidone Synthesis; Stage #2: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione In ethanol at 80℃; for 24h; Biginelli Pyrimidone Synthesis;	67%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → 3,5-bis<β-(4-hydroxy-3-methoxyphenyl)ethyl>pyrazole (113464-93-0)

Conditions	Yield
With hydrazine hydrate; acetic acid In ethanol; butan-1-ol at 60℃; for 24h;	65%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 2-amino-5-nitrobenzophenone (1775-95-7) → 1-(2-(4-hydroxy-3-methoxyphenethyl)-6-nitro-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one (1408335-43-2)

Conditions	Yield
With trifluoroacetic acid at 100℃; for 2h;	65%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 3-nitro-benzaldehyde (99-61-6) + urea (57-13-6) → C29H29N3O8 (1432038-13-5)

Conditions	Yield
Stage #1: 3-nitro-benzaldehyde; urea With copper(ll) sulfate pentahydrate In ethanol at 80℃; for 0.25h; Biginelli Pyrimidone Synthesis; Stage #2: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione In ethanol at 80℃; for 24h; Biginelli Pyrimidone Synthesis;	59%

1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) + 4-methoxy-benzaldehyde (123-11-5) → 1,1'-(2,6-bis(4-hydroxy-3-methoxyphenethyl)-4-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-diyl)bis-(3-(4-hydroxy-3-methoxyphenyl)propan-1-one) + (Z)-5-amino-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one

Conditions	Yield
Stage #1: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione; 4-methoxy-benzaldehyde With toluene-4-sulfonic acid In ethanol at 80℃; for 0.333333h; Hantzsch Dihydropyridine Synthesis; Molecular sieve; Stage #2: With ammonium acetate In ethanol at 80℃; for 24h; Hantzsch Dihydropyridine Synthesis; Molecular sieve;	A 10% B 54%

[iridium(III)(μ-chloro)(2-phenylpyridine)2]2 + 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione (36062-04-1) → C43H39IrN2O6

Conditions	Yield
Stage #1: 1,7-bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-dione With sodium methylate In methanol at 0℃; for 1h; Stage #2: [iridium(III)(μ-chloro)(2-phenylpyridine)2]2 In methanol for 24h; Reflux;	54%

Upstream product

• 458-37-7 curcumin 
• 98885-93-9 curcumin 
• 121-33-5 vanillin 
• 123-54-6 acetylacetone 
• 115945-70-5 glucose 
• 458-37-7 curcumin 
• 52199-86-7 1,7-bis(4’-acetoxy-3’-methoxyphenyl)-3,5-heptadione 
• 1135-24-6 (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid 
• 1135-23-5 3-(4-hydroxy-3-methoxyphenyl)propionic acid 
• 1135-24-6 3-(4-hydroxy-3-methoxyphenyl)acrylic acid 

Downstream Products

• 113464-93-0 3,5-bis<β-(4-hydroxy-3-methoxyphenyl)ethyl>pyrazole 
• 36062-05-2 hexahydrocurcumin 
• 36062-07-4 3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane 
• 113465-11-5 tetrahydrocurcumin isoxazole 
• 1408335-41-0 1-(2-(4-hydroxy-3-methoxyphenethyl)-4-methylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one 
• 1408335-42-1 1-(2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one 
• 1408335-43-2 1-(2-(4-hydroxy-3-methoxyphenethyl)-6-nitro-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one 
• 1408335-44-3 1-(6-chloro-2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one 
• 1408335-45-4 1-(6-amino-2-(4-hydroxy-3-methoxyphenethyl)-4-phenylquinolin-3-yl)-3-(4-hydroxy-3-methoxyphenyl)propan-1-one 
• 1432038-10-2 6-(4-hydroxy-3-methoxyphenethyl)-5-(3-(4-hydroxy-3-methoxyphenyl)propanoyl)-4-phenyl-3,4-dihydropyrimidin-2(1H)-one 
• 1432038-13-5 C₂₉H₂₉N₃O₈ 
• 1432038-14-6 C₂₉H₂₉N₃O₈ 
• 1432038-15-7 C₂₉H₃₀N₂O₇ 
• 1432038-16-8 C₃₀H₃₂N₂O₇ 

Relevant articles and documents

Neuroprotective effects of Tetrahydrocurcumin against glutamate-induced oxidative stress in hippocampal HT22 cells

In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.

Structural and Biochemical Characterization of the Curcumin-Reducing Activity of CurA from Vibrio vulnificus

Curcumin is a yellow-colored ingredient in dietary spice turmeric (Curcuma longa Linn). This nontoxic polyphenol has antitumor, anti-inflammatory, apoptotic, and antioxidant activities. The ingested curcumin is reduced to multihydrated forms with more potent therapeutic potentials by the curcumin reductase (CurA) from commensal Escherichia coli. In this study, we demonstrated that Vibrio vulnificus CurA (VvCurA) with 87% sequence similarity to the E. coli CurA exhibits the curcumin-reducing activity through spectrophotometric detection of NADPH oxidation and high performance liquid chromatographic analysis of curcumin consumption and product generation. Afterward, we determined the crystal structures of VvCurA and the VvCurA/NADPH complex, and made the in silico model of the VvCurA/NADPH/curcumin ternary complex through induced fit docking. Based on structural information, active site residues that play critical roles in catalysis have been identified and characterized by mutational and kinetic studies, leading us to propose the reaction mechanism of CurA.

NOVEL TETRAHYDROCURCUMIN COMPOSITIONS, METHODS OF MAKING, AND METHODS OF USING THE SAME

The present invention relates to novel tetrahydrocurcumin (THCu) compositions, novel methods of manufacturing, and methods of using these compositions for therapeutic applications. The novel synthetic pathway(s) result in THCu compositions that generally lack hexahydrocurcumin (HHC), and include an improved impurity profile with reduced additional species that are generally present in hydrogenated curcumin compositions.

Pharmacokinetics-driven evaluation of the antioxidant activity of curcuminoids and their major reduced metabolites—a medicinal chemistry approach

Curcuminoids are the main bioactive components of the well-known Asian spice and traditional medicine turmeric. Curcuminoids have poor chemical stability and bioavailability; in vivo they are rapidly metabolized to a set of bioreduced derivatives and/or glucuronide and sulfate conjugates. The reduced curcuminoid metabolites were also reported to exert various bioactivities in vitro and in vivo. In this work, we aimed to perform a comparative evaluation of curcuminoids and their hydrogenated metabolites from a medicinal chemistry point of view, by determining a set of key pharmacokinetic parameters and evaluating antioxidant potential in relation to such properties.Reduced metabolites were prepared from curcumin and demethoxycurcumin through continuous-flow hydrogenation. As selected pharmacokinetic parameters, kinetic solubility, chemical stability, metabolic stability in human liver microsomes, and parallel artificial membrane permeability assay (PAMPA)-based gastrointestinal and blood-brain barrier permeability were determined. Experimentally determined logP for hydrocurcumins in octanol-water and toluene-water systems provided valuable data on the tendency for intramolecular hydrogen bonding by these compounds. Drug likeness of the compounds were further evaluated by a in silico calculations. Antioxidant properties in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbance capacity (ORAC) assays were comparatively evaluated through the determination of ligand lipophilic efficiency (LLE). Our results showed dramatically increased water solubility and chemical stability for the reduced metabolites as compared to their corresponding parent compound. Hexahydrocurcumin was found the best candidate for drug development based on a complex pharmacokinetical comparison and high LLE values for its antioxidant properties. Development of tetrahydrocurcumin and tetrahydro-demethoxycurcumin would be limited by their very poor metabolic stability, therefore such an effort would rely on formulations bypassing first-pass metabolism.

New insights towards 1,4-benzodiazepines from curcumin. Design, synthesis and antimicrobial activities

Background: Curcumin is a safe, versatile natural product with unlimited number of biological activities and a precursor for various heterocyclic compounds. Objective: The present study was aimed to the development of a curcumin based antimicrobial reagent with high potency against gram-positive and gram-negative bacteria. Methods: Herein we report a simple and convenient one step method for synthesizing a series of 1,4-benzodiazepines via condensation cyclization reaction between curcumin and various 1,2- phenylenediamine in refluxed ethanol. Results: A series of new 1,4-benzodiazepins were synthesized and their structures were supported by FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. Synthesized 1,4-benzodiazepins were evaluated for their in vitro antimicrobial activity against gram positive (S. aureus and S. epidermidis) and gram negative (E. coli and P. aeruginosa) bacteria. They exhibited low to high potency against the tested organisms. In particular, dichlorinated 1,4-benzodiazepine 9 exhibited a remarkable potency against the gram-positive bacteria S. aureus (MIC: 3.125 μg mL?1, MBC: 12 μg mL?1). It showed a higher potency than most of the tested reference drugs. Compound 9 showed the medium activity against E. Coli. Genotoxic study revealed that, benzodiazepines 9 attacked the DNA of E. Coli strains and damaged it. The potency of compound 9, could be attributed to the multiple chlorine atoms present on the aromatic ring. Conclusion: Some of the synthesized curcumin based benzodiazepines showed excellent potency against gram positive bacteria. These benzodiazepines could be a great candidate as a future antimicrobial agent.

Preparation method of tetrahydrocurcumin and intermediate thereof

The invention provides a preparation method of tetrahydrocurcumin and an intermediate thereof, and the preparation method of the intermediate comprises the following steps: step a, in the presence ofalkali, reacting a compound (IV) with an acetylation reagent in a solvent to obtain a compound (III); b, in the presence of a catalyst and a solvent, the compound (III) and hydrogen or a hydrogen donor are subjected to a reduction reaction to obtain a compound (II), namely the tetrahydrocurcumin intermediate; and the tetrahydrocurcumin preparation method comprises the step that acetyl is removed from the compound (II) in the solvent in the presence of alkali to obtain a compound (I), namely tetrahydrocurcumin. The selectivity of the diacetyl curcumin reduction reaction is far superior to thatof direct reduction of curcumin, and the yield is high; the method is simple and convenient in purification and high in product content, and hardly contains curcumin, hexahydrocurcumin and octahydrocurcumin; the method disclosed by the invention is simple and feasible to operate, stable and durable in process, easy to control, easy to amplify and convenient in post-reaction treatment, and can be economically and conveniently used for industrial production.

Novel preparation method for tetrahydrocurcumin

The invention provides a novel preparation method for tetrahydrocurcumin. Curcumin, 2,6-dimethyl-3,5-diethyl ester-1,4-dihydropyridine (dihydropyridine for short) and ethanol are used as raw materials, and palladium on carbon is used as a catalyst for a reflux reaction. The preparation method comprises the following steps: putting the raw materials into a reaction bottle, performing a reflux reaction and filtering, and conducting evaporating under reduced pressure to remove ethanol to obtain a mixture; and adding diluted hydrochloric acid into the obtained mixture for washing, then carrying out decoloring by using activated carbon, removing the activated carbon, and evaporating ethanol under reduced pressure again to obtain tetrahydrocurcumin. According to the preparation method of tetrahydrocurcumin, dihydropyridine is adopted as a hydrogen source, reaction raw materials are non-toxic and pollution-free, the utilization rate of equipment and safety are high, the obtained product onlyneeds simple treatment, and the method is suitable for industrial production.

NOVEL TETRAHYDROCURCUMIN COMPOSITIONS, METHODS OF MAKING, AND METHODS OF USING THE SAME

The present invention relates to novel tetrahydrocurcumin (THCu) compositions, novel methods of manufacturing, and methods of using these compositions for therapeutic applications. The novel synthetic pathway(s) result in THCu compositions that generally lack hexahydrocurcumin (HHC), and include an improved impurity profile with reduced additional species that are generally present in hydrogenated curcumin compositions.

Use of curcumin derivative

The invention provides the use of a curcumin derivative. The use of the curcumin derivative shown in a formula I (please see the specification for the formula), or salts of the curcumin derivative inthe preparation of drugs of anti-inflammatory diseases and/or a COX inhibitor is particularly provided. The curcumin derivative has good COX inhibitory activity and anti-inflammatory activity and canbe used for preparing the COX inhibitor and anti-inflammatory drugs. Compound 6 and compound 7 have the best effects on COX-2 inhibitory activity and anti-inflammatory activity and can be used for preparing a COX-2 inhibitor and the anti-inflammatory drugs.

A preparation method of the four mammalian keratinous tissue

The invention provides a method for preparing tetrahydrocurcumin. The method for preparing tetrahydrocurcumin comprises the following steps: with curcumin and ethanol as raw materials and with platinum-iron-nickel hydroxide composite nano particles as a catalyst, reacting in a reaction bottle under a room temperature condition, concentrating, refrigerating, standing and crystallizing to prepare tetrahydrocurcumin. According to the method for preparing tetrahydrocurcumin, a novel catalyst is adopted to directly reduce curcumin into tetrahydrocurcumin at the room temperature, the reaction time is short, the yield, the equipment utilization rate and the safety are high, the after-treatment of an obtained product is simple, the method is suitable for industrial production, and the yield is greatly improved.