479-90-3

Basic information

• Product Name: ARTEMISETIN(P)
• Synonyms: ARTEMISETIN(P);2-(3,4-Dimethoxyphenyl)-5-hydroxy-3,6,7-trimethoxy-4H-1-benzopyran-4-one;3,3',4',6,7-Pentamethoxy-5-hydroxyflavone;Erianthin;ArteMitin;2-(3,4-dimethoxyphenyl)-5-hydroxy-3,6,7-trimethoxy-4H-chromen-4-one;Artemisetin, 98%, from Artemisia argyi
• CAS NO: 479-90-3
• Molecular Formula: C₂₀H₂₀O₈
• Molecular Weight: 388.368
• EINECS: 200-258-5
• Product Categories: Active Pharmaceutical Ingredients;sy;Flavonoids
• Mol File: 479-90-3.mol
• Article Data: 7

Chemical Properties

• Melting Point: 261～264℃
• Boiling Point: 588.8°Cat760mmHg
• Flash Point: 208.9°C
• Appearance: /
• Density: 1.37g/cm³
• Vapor Pressure: 1.84E-14mmHg at 25°C
• Refractive Index: 1.607
• Storage Temp.: 2-8°C
• PKA: 6.12±0.40(Predicted)
• CAS DataBase Reference: ARTEMISETIN(P)(CAS DataBase Reference)
• NIST Chemistry Reference: ARTEMISETIN(P)(479-90-3)
• EPA Substance Registry System: ARTEMISETIN(P)(479-90-3)

Safety Data

• Hazardous Substances Data: 479-90-3(Hazardous Substances Data)

Usage

General Description

ARTEMISETIN(P) is an antimalarial drug that contains the active ingredient artemisinin, which is derived from the sweet wormwood plant. Artemisinin and its derivatives are known for their potent antimalarial properties and are widely used in the treatment of uncomplicated malaria. ARTEMISETIN(P) is available in various formulations such as tablets, capsules, and injections, and is commonly used in combination with other antimalarial drugs to prevent the development of drug resistance. It is effective in killing the malaria parasites at all stages of their life cycle, making it a crucial tool in the fight against malaria. However, like other antimalarial drugs, ARTEMISETIN(P) can also have side effects such as nausea, vomiting, and dizziness, and should be used with caution, especially in pregnant women and young children.

InChI:InChI=1/C20H20O8/c1-23-11-7-6-10(8-12(11)24-2)18-20(27-5)17(22)15-13(28-18)9-14(25-3)19(26-4)16(15)21/h6-9,21H,1-5H3

Synthetic route

3,5,6,7,3',4'-Hexamethoxyflavon (1251-84-9) → artemetin (479-90-3)

Conditions	Yield
With aluminum tri-bromide In acetonitrile at 0 - 5℃; for 0.333333h;	95%
With boron trichloride In tetrahydrofuran at -78℃;	79%

5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one (23370-16-3) → artemetin (479-90-3)

Conditions	Yield
With sodium hydride; methyl iodide In N,N-dimethyl-formamide at 20℃;	32%

chrysosplenol C (59171-25-4) + methyl iodide (74-88-4) → artemetin (479-90-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 5 - 10℃;	32%

2.6-dioxy-3.4.ω-trimethoxy-acetophenone + anhydride of/the/ veratric acid → artemetin (479-90-3)

Conditions	Yield
With sodium 3,4-dimethoxybenzoate at 180 - 190℃; Verseifen des Reaktionsprodukts mit waessrig-alkoholischer Kalilauge;

diazomethane (186581-53-3, 908094-01-9) + quercetagetin → artemetin (479-90-3)

Conditions	Yield
With diethyl ether; dichloromethane

dimethyl sulfate (77-78-1) + quercetagetin → artemetin (479-90-3)

Conditions	Yield
With potassium carbonate; acetone

methyl iodide (74-88-4) + quercetagetin → 3,5,6,7,3',4'-Hexamethoxyflavon (1251-84-9) + artemetin (479-90-3)

Conditions	Yield
With methanol Behandeln der Reaktions-Loesung mit methylalkoholischer Kalilauge;
With methanol Behandeln der Reaktionsloesung mit methylalkoholischer Kalilauge;

1-(3,6-dihydroxy-2,4-dimethoxy-phenyl)-2-methoxy-ethanone (14639-73-7) → artemetin (479-90-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) potassium benzoate, 2.) K2CO3 / 1.) 170/180 deg C, 8 h, 2.) acetone, reflux, 2.5-4 h 2: 95 percent / AlBr3 / acetonitrile / 0.33 h / 0 - 5 °C View Scheme

3,4-dimethoxybenzoic anhydride (24824-54-2) + 2.4.6-trioxy-propiophenone → artemetin (479-90-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) potassium benzoate, 2.) K2CO3 / 1.) 170/180 deg C, 8 h, 2.) acetone, reflux, 2.5-4 h 2: 95 percent / AlBr3 / acetonitrile / 0.33 h / 0 - 5 °C View Scheme

5,6,7,4'-tetramethoxyflavone (1168-42-9) + sinensetin (2306-27-6) + tangeritin (481-53-8) + 3,5,6,7,3',4'-Hexamethoxyflavon (1251-84-9) + nobiletin (478-01-3) + 3,3',4',5,6,7,8-heptamethoxyflavone (1178-24-1) → gardenin B (2798-20-1) + 5-hydroxy-4',6,7-trimethoxyflavone (19103-54-9) + 5-desmethylsinensetin (21763-80-4) + artemetin (479-90-3) + 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (2174-59-6) + 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (1176-88-1)

Conditions	Yield
With hydrogenchloride; ethanol at 80℃; for 18 - 70h; Product distribution / selectivity; Heating / reflux;
With hydrogenchloride; ethanol; water at 80℃; for 18h; Conversion of starting material; Heating / reflux;
With ethanol; water for 24h; Product distribution / selectivity; Heating / reflux;

...Expand

patuletin (519-96-0) + dimethyl sulfate (77-78-1) → artemetin (479-90-3)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 96h;	20 mg

artemetin (479-90-3) + p-toluenesulfonyl chloride (98-59-9) → Toluene-4-sulfonic acid 2-(3,4-dimethoxy-phenyl)-3,6,7-trimethoxy-4-oxo-4H-chromen-5-yl ester (124909-90-6)

Conditions	Yield
With potassium carbonate In acetone Heating;	95%

artemetin (479-90-3) → 2-(3,4-dimethoxy-phenyl)-5,8-dihydroxy-3,6,7-trimethoxy-chromen-4-one (110492-41-6)

Conditions	Yield
With pyridine; potassium hydroxide; dipotassium peroxodisulfate Erwaermen des Reaktionsgemisches mit wss. Salzsaeure und Natriumsulfit;

artemetin (479-90-3) + acetic anhydride (108-24-7) → 5-acetoxy-2-(3,4-dimethoxy-phenyl)-3,6,7-trimethoxy-chroman-4-one (95135-98-1)

Conditions	Yield
With pyridine

artemetin (479-90-3) → 3,5-dihydroxy-6,7,3′,4′-tetramethoxyflavone (57296-14-7)

Conditions	Yield
With aluminium trichloride for 24h; Heating;	15 mg
With aniline hydrochloride
Multi-step reaction with 3 steps 1: 95 percent / K2CO3 / acetone / Heating 2: 91 percent / AlBr3 / acetonitrile / 1 h / Ambient temperature 3: 88 percent / K2CO3 / methanol / 2 h / Heating View Scheme

artemetin (479-90-3) → 3,5-dihydroxy-6,7,3′,4′-tetramethoxyflavone (57296-14-7) + 3,5-dihydroxy-7,8,3',4'-tetramethoxyflavone (72620-07-6)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	A 30 mg B 20 mg

artemetin (479-90-3) → Acetic acid 3-acetoxy-2-(3,4-dimethoxy-phenyl)-6,7-dimethoxy-4-oxo-4H-chromen-5-yl ester (104055-81-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / K2CO3 / acetone / Heating 2: 91 percent / AlBr3 / acetonitrile / 1 h / Ambient temperature 3: 88 percent / K2CO3 / methanol / 2 h / Heating 4: pyridine / 24 h / Ambient temperature View Scheme

artemetin (479-90-3) → Toluene-4-sulfonic acid 2-(3,4-dimethoxy-phenyl)-3-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-5-yl ester (124909-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / K2CO3 / acetone / Heating 2: 91 percent / AlBr3 / acetonitrile / 1 h / Ambient temperature View Scheme

artemetin (479-90-3) → 3,3',4',5,6,7,8-heptamethoxyflavone (1178-24-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous KOH-solution; pyridine; aqueous potassium peroxo disulfate solution / Erwaermen des Reaktionsgemisches mit wss. Salzsaeure und Natriumsulfit 2: acetone; potassium carbonate View Scheme

Upstream product

• 1168-42-9 5,6,7,4'-tetramethoxyflavone 
• 2306-27-6 sinensetin 
• 481-53-8 tangeritin 
• 1251-84-9 3,5,6,7,3',4'-Hexamethoxyflavon 
• 478-01-3 nobiletin 
• 1178-24-1 3,3',4',5,6,7,8-heptamethoxyflavone 
• 65602-54-2 2'-hydroxy-3,4,4',5',6'-pentamethoxychalcone 
• 22248-14-2 6-hydroxy-2,3,4-trimethoxyacetophenone 
• 86-81-7 3,4,5-trimethoxy-benzaldehyde 
• 642-71-7 3,4,5-trimethoxyphenol 
• 23370-16-3 5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one 
• 24824-54-2 3,4-dimethoxybenzoic anhydride 
• 14639-73-7 1-(3,6-dihydroxy-2,4-dimethoxy-phenyl)-2-methoxy-ethanone 
• 74-88-4 methyl iodide 

Downstream Products

• 110492-41-6 2-(3,4-dimethoxy-phenyl)-5,8-dihydroxy-3,6,7-trimethoxy-chromen-4-one 
• 104055-81-4 Acetic acid 3-acetoxy-2-(3,4-dimethoxy-phenyl)-6,7-dimethoxy-4-oxo-4H-chromen-5-yl ester 
• 124909-97-3 Toluene-4-sulfonic acid 2-(3,4-dimethoxy-phenyl)-3-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-5-yl ester 
• 1178-24-1 3,3',4',5,6,7,8-heptamethoxyflavone 
• 57296-14-7 3,5-dihydroxy-6,7,3′,4′-tetramethoxyflavone 
• 72620-07-6 3,5-dihydroxy-7,8,3',4'-tetramethoxyflavone 
• 124909-90-6 Toluene-4-sulfonic acid 2-(3,4-dimethoxy-phenyl)-3,6,7-trimethoxy-4-oxo-4H-chromen-5-yl ester 
• 95135-98-1 5-Acetoxy-3,6,7,3',4'-pentamethoxy-flavon 

Relevant articles and documents

Synthesis and anti-proliferative activities of 5,6,7-trimethoxyflavones and their derivatives

A series of 5,6,7-trimethoxyflavones 1a-1g and their derivatives 2a-2g, 3a-3d, 4 and 5, including the natural products 5,6,7-trimethoxy-4’-hydroxyflavone (1a), 5,6,7,3’,4’ -pentamethoxyflavone (sinensetin, 1 b), 5,6,7-trimethoxy-3’,4’-methyl enedioxy flavone (1c), 5,6,7,3’-tetramethoxy-4,5’-methylenedioxyflavone (1e), 5,6,7, 3’,4’,5’-hextamethoxyflavone (1 g), 5-hydroxy-3,4,2’,3’,4’-pentamethoxy chal-cone (2 b), 5,4’-dihydroxy-6,7-dimethoxy flavone (cirsimaritin, 3a) and 5-hydroxy-6,7,3’, 4’-tetramethoxyflavone (5-demethylsinensetin, 3 b), 3,5,6,7,3’,4’-hexamethoxyflavone (3-methoxysinensetin, 4) and 5’-hydroxy-3,6,7,3’,4’-pentamethoxyflavone (5) were synthesized. Their anti-proliferative activity in?vitro was evaluated against a panel of four human cancer cell lines (Aspc-1, HCT-116, HepG-2 and SUN-5) by the CTG assay. The results showed that most of the synthetic compounds exhibited moderate to high anti-proliferative activities. In particular, compound 3c possess IC50 (5.30 μM) values below 10 μM against Aspc-1 cells and are worthy of further investigation.

Exploration of Pharmacophore in Chrysosplenol C as Activator in Ventricular Myocyte Contraction

Chrysosplenol C (4',5,6-trihydroxy-3,3',7-trimethoxyflavone) isolated from Miliusa balansae has unique structural features as a reversible inotropic agent independent of β-adrenergic signaling and with selective activation of cardiac myosin ATPase. Hence, a series of chrysosplenol analogues were synthesized and explored for identification of pharmacophore that is essential for the increasing contractility in rat ventricular myocytes. Analogue 7-chloro-2-(3-hydroxyphenyl)-3-methoxy-4H-chromen-4-one showed highly potent contractility (54.8% at 10 μM) through activating cardiac myosin ATPase (38.7% at 10 μM). Our systematic structure-activity relationship study revealed that flavonoid nucleus of chrososplenol C appears to be an essential basic skeleton and hydrophobic substituent at position 7 of chromenone such as methoxy or chloro enhances the activity. Additionally, our ATPase study suggested that these chrysosplenol analogues have selectivity toward cardiac myosin activation. Thus, the novel flavonone with 3-/7-hydrophobic substituent and 3'-hydrogen bonding donor function is a novel scaffold for discovery of a new positive inotropic agent.

PROCESS TO PREPARE FLAVONES

The present invention relates to the field of flavor ingredients. More particularly it provides, a process for making 5- hydroxy -polyitιethoxy-f lavones (5-OH-PMF) (I) or improving the organoleptic properties of natural polymethoxy-f lavones (PMF) . The invention's process comprises treating flavones (II) in the presence of a HCl solution in a non-acidic and non -aqueous solvent. (I) (II).