568-72-9

Basic information

• Product Name: Tanshinone IIA
• Synonyms: AKOS NCG1-0066;3,8,8-TRIMETHYL-8,9,10,11-TETRAHYDROPHENANTHRO[1,2-B]FURAN-1,2-DIONE;1,6,6-TRIMETHYL-6,7,8,9-TETRAHYDRO-PHENANTHRO[1,2-B]FURAN-10,11-DIONE;TANSHINONE IIA;TANSHINONES IIA;tanshiones;Tanshionesiia;TANSHINONE IIA 98%
• CAS NO: 568-72-9
• Molecular Formula: C₁₉H₁₈O₃
• Molecular Weight: 294.34
• Product Categories: Plant Oils, Toxins, Phenolic Acids & Derivatives;The group of Danshen;Plant extract;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 568-72-9.mol
• Article Data: 7

Chemical Properties

• Melting Point: 196.0 to 200.0 °C
• Boiling Point: 480.7 °C at 760 mmHg
• Flash Point: 236.4 °C
• Appearance: Cherry crystal
• Density: 1.209 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.603
• Storage Temp.: 2-8°C
• Solubility: methanol: soluble5mg/mL, clear, red-orange to red
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Tanshinone IIA(CAS DataBase Reference)
• NIST Chemistry Reference: Tanshinone IIA(568-72-9)
• EPA Substance Registry System: Tanshinone IIA(568-72-9)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• RTECS: SF8282695
• Hazardous Substances Data: 568-72-9(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 568-72-9 differently. You can refer to the following data:
1. Tanshinone IIA mainly exists in the roots of Salvia miltiorrhiza Bge. Traditional Chinese medicine Danshen, slightly cold and bitter, is often used for activating blood circulation and eliminating stasis in Chinese medicine. It can also promote blood circulation, open the energy channels, calm the heart, cool the blood, relieve swelling, remove twinge in the heart and stomach, and remove carbuncle and erysipelas. It is classified as high grade in Shen Nong’s Herbal Classic. It has been used as a traditional Chinese medicine in clinical practice for thousands of years. And it is not only recorded in the leading medical works through the ages but also in CP and USP.
2. Tanshinone IIA (TSA) is a major lipophilic component of extracts from the root of S. miltiorrhiza, used widely in Chinese herbal medicine. It has anti-inflammatory activity, inhibiting production of TNF-α, IL-1β, IL-6, NO, INFγ, and expression of iNOS, and IL-12. It blocks human aortic smooth muscle cell migration, inhibits MMP-9 activity, and interferes with PI3K/Akt and ERK1/2 signaling pathways. It is cytotoxic to various cancer cells including A549 lung cancer cells and leukemia cells.Reduction of TSA by NAD(P)H:quinone oxidoreductase (NQO1) generates an unstable intermediate resulting in reactive oxygenase species-mediated apoptotic cell death.

Chemical Properties

Orange powder

Physical properties

Appearance: brick-red crystalline powder. Melting point: 209–210?°C. Solubility: absorbs moisture easily, very soluble in hot water, slightly soluble in methanol or ethanol, and practically insoluble in chloroform

History

The study of the chemical composition of Salvia miltiorrhiza began in the 1930s. Japanese scholars first extracted three kinds of liposoluble components from Danshen. They are tanshinones I, II, and III.

Uses

Different sources of media describe the Uses of 568-72-9 differently. You can refer to the following data:
1. Tanshinone IIA is a derivative of Tanshinone and acts as a potential inhibitor of tumor growth in vivo. Also maintains vasodilating activity in vivo.
2. antineoplastic, bone resorption inhibitor, antiproliferative, apoptosis inducer

Synthesis Reference(s)

Journal of the American Chemical Society, 111, p. 1522, 1989 DOI: 10.1021/ja00186a070

Biochem/physiol Actions

Phenanthrenequinone constituent of Chinese medicinal herb Danshen (Salvia miltiorrhiza). Anti-inflammatory. Antioxidant. Cytotoxic against a variety of cell lines, inlcuding human glioma cells.

Pharmacology

Long-term researches show that tanshinone exhibits a variety of pharmacological effects, such as the protection of the cardiovascular system, anti-infective effects, and antioxidant effects. As for the domestic pharmacological study of tanshinone IIA, it was first started in the Shanghai Institute of Chinese Medicine. Professor Ding Guangsheng discussed the cardiovascular effects of tanshinone IIA.?He found that intraperitoneal injection of tanshinone IIA sodium sulfonate (200?mg/kg) significantly prolonged the survival time of mice under hypoxia atmosphere, and an increase in cardiac output was observed in a dog under anesthesia with a one-time intravenous injection of 20? mg/kg . In recent years, the mechanism of tanshinone IIA is increasingly brought to further research. Tanshinone IIA can increase the activity of superoxide dismutase (SOD) and interfere with the pathological process of many diseases, especially in cardiovascular diseases. It can attenuate the damages from the reactive oxygen species to vascular endothelial cells, lower the risk of atherosclerosis, and reduce the formation of atheromatous plaque. tumor cells and the expression of various genes connected with the proliferation, differentiation, and apoptosis of tumor cells. It may also have something to do with the inhibition of telomerase activity in tumor cells, changes in antigen expression on tumor cell surface, etc.

Clinical Use

Tanshinone IIA is a diterpenoid quinone liposoluble ingredient of high content, and its chemical structure is the most representative in Danshen. In addition to tanshinone IIA sodium sulfonate, there are a variety of preparations of Salvia common ketone used clinically, such as tanshinone tablets, tanshinone capsules, tanshinone injection, Danshen Shuxin capsule, compound Danshen soft capsules, and compound Danshen particles.

Cytotoxicity

IC50 (μg/mL): 0.59 (A549), 0.81 (TOV-21G) and 1.9 (MIAPaCa-2), NS (MV-3)(Chang et al. 2013; Fronza et al. 2011).IC50 (μg/mL): 2.97 (HeLa), 2.71 (KB-3-1),>2.94 (NCI-H460), 2.62 (PC3), 2.94(MCF-7), 1.62 (K562)(Wu et al. 2014)

References

1) Kang et al. (2000), Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza; Immunopharmacology, 49 355 2) Sung et al. (1999), Tanshinone IIA, an ingredient of Salvia miltiorrhiza BUNGE, induces apoptosis in human leukemia cell lines through the activation of caspase-3; Exp. Mol. Med., 31 174 3) Park et al. (1999), Suppression of AP-1 Activity by Tanshinone and Cancer Cell Growth Inhibition; Bull. Korean Chem. Soc., 20 925

InChI:InChI=1/C19H20O3/c1-10-9-22-18-12-6-7-13-11(5-4-8-19(13,2)3)15(12)17(21)16(20)14(10)18/h6-7,10H,4-5,8-9H2,1-3H3

Synthetic route

(+/-)-cryptotanshinone (17545-07-2, 35825-57-1) → tanshinone IIA (568-72-9)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In benzene at 20℃;	95%

Cryptotanshinone (35825-57-1) → tanshinone IIA (568-72-9)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In benzene at 25℃; for 42h;	91%

C25H22O4 → tanshinone IIA (568-72-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen In tetrahydrofuran	40%

methyl 2-(1-methoxycarbonyl-5,5-dimethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-4-methylfuran-3- carboxylate → tanshinone IIA (568-72-9)

Conditions	Yield
With sodium In tetrahydrofuran at 50℃; for 1h; Inert atmosphere;	40%

6,6-dimethyl-1-vinylcyclohex-1-ene (18238-29-4) + 4,5-dihydro-3-methylbenzo[1,2-b]furan-4,5-dione (113297-21-5) → tanshinone IIA (568-72-9) + 3,8,8-Trimethyl-8,9,10,11-tetrahydro-phenanthro[4,3-b]furan-4,5-dione (118950-00-8)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone 1) neat, ultrasound, 45 deg C, 2h, (or benzene, 12h, reflux), 2) benzene, 12h, reflux; Yield given. Multistep reaction. Yields of byproduct given;
Yield given. Multistep reaction. Yields of byproduct given;
With 2,3-dicyano-5,6-dichloro-p-benzoquinone 1) benzene, reflux, 12h, (or ultrasonification, 45 deg C, 2h), 2) benzene, 12h, reflux; Yield given. Multistep reaction. Yields of byproduct given;

1-bromo-4-methylpent-3-ene (2270-59-9) → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) n-BuLi, TMEDA / 1.) hexane, 45 deg C, 30 min, 2.) THF, 55-60 deg C, 20 h 2: 97 percent / AlCl3 / CH2Cl2 / 0.25 h / 0 °C 3: 95 percent / BBr3 / CH2Cl2 / 4 h / -78 - 25 °C 4: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 5: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 6: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 7: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 8: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 9: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 10: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

2-bromoanisole (578-57-4) + BBr3 → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 93 percent / PdCl2(dppf) / tetrahydrofuran / 15 h / Heating 2: 97 percent / AlCl3 / CH2Cl2 / 0.25 h / 0 °C 3: 95 percent / BBr3 / CH2Cl2 / 4 h / -78 - 25 °C 4: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 5: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 6: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 7: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 8: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 9: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 10: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

5,5-dimethyl-5,6,7,8-tetrahydronaphthalen-1-ol (171979-69-4) → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 7 steps 1: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 2: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 3: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 4: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 5: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 6: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 7: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

1,1-dimethyl-5-methoxytetralin (33214-70-9) → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 8 steps 1: 95 percent / BBr3 / CH2Cl2 / 4 h / -78 - 25 °C 2: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 3: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 4: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 5: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 6: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 7: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 8: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

methoxybenzene (100-66-3) + 2-chloro-decalin → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) n-BuLi, TMEDA / 1.) hexane, 45 deg C, 30 min, 2.) THF, 55-60 deg C, 20 h 2: 97 percent / AlCl3 / CH2Cl2 / 0.25 h / 0 °C 3: 95 percent / BBr3 / CH2Cl2 / 4 h / -78 - 25 °C 4: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 5: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 6: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 7: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 8: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 9: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 10: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

4-methylpent-3-enylzinc(II) bromide → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 93 percent / PdCl2(dppf) / tetrahydrofuran / 15 h / Heating 2: 97 percent / AlCl3 / CH2Cl2 / 0.25 h / 0 °C 3: 95 percent / BBr3 / CH2Cl2 / 4 h / -78 - 25 °C 4: 87 percent / DMAP / pyridine / 1.) 0 deg C -> 25 deg C, 1 h, 2.) 25 deg C, 48 h 5: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 6: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 7: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 8: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 9: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 10: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

5,6,7,8-tetrahydro-3-hydroxy-2-[(1R)-2-hydroxy-1-methylethyl]-8,8-dimethyl-1,4-phenanthrenedione (109664-02-0) → tanshinone IIA (568-72-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 2: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

1,1-dimethyl-5-tetralyl trifluoromethanesulfonate (171979-71-8) → tanshinone IIA (568-72-9)

Conditions

Yield

Multi-step reaction with 6 steps 1: 71 percent / LiCl, 4A sieves, Me4Sn, 2,6-di-tert-butylhydroxytoluene / PdCl2(dppf) / dimethylformamide / 12 h / 90 °C / 2585.7 Torr 2: 1.) LiHMDS, 2,2,2-trifluoroethyl trifluoroacetate, 2.) MsN3, Et3N / 1.) THF, -78 deg C, 45 min, 2.) MeCN, H2O, 25 deg C, 6 h 3: 64 percent / benzene / 24 h / Ambient temperature; Irradiation 4: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 5: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 6: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

3-((S)-1-((tert-butyldimethylsilyl)oxy)-2-propyl)-7,7-dimethyl-4-hydroxy-2-((triisopropylsilyl)oxy)-7,8,9,10-tetrahydrophenanthrene (171979-72-9) → tanshinone IIA (568-72-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 84 percent / n-Bu4NF, O2 / tetrahydrofuran / 40 h / 25 °C 2: 100 percent / conc. H2SO4 / ethanol / 0.75 h / 25 °C 3: 91 percent / DDQ / benzene / 42 h / 25 °C View Scheme

tanshinone IIA (568-72-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 1,6,6-trimethyl-6,7,8,9,10,11-hexahydro-10,11-dioxophenanthro[1,2-b]furan-2-carbaldehyde

Conditions	Yield
With trichlorophosphate at 20℃; for 2h;	100%
With trichlorophosphate at 20℃; for 2.5h; Vilsmeier-Haack Formylation;	97.3%
With trichlorophosphate at 70 - 80℃; for 2h;	67%

tanshinone IIA (568-72-9) → 2-iodo-10,11-dioxo-1,6,6-trimethyl-6,7,8,9,10,11-hexahydro-phenanthro[1,2-b]furan

Conditions	Yield
With potassium iodate; acetic acid; potassium iodide In water at 80℃; for 1h;	98.99%
With N-iodo-succinimide; acetic acid In dichloromethane at -40℃; for 6h;

tanshinone IIA (568-72-9) → sodium 1,6,6-trimethyl-10,11-dioxo-8,9-dihydro-7Hnaphtho[1,2-g][1]benzofuran-2-sulfonate

Conditions	Yield
With sodium hydrogen sulfate; acetic anhydride; 1,4,7,10-tetraoxa-15-azacyclopentadecane at 20℃; for 1h; Reagent/catalyst; Temperature; Green chemistry;	96%
Stage #1: tanshinone-IIA With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 100℃; Stage #2: With sodium hydroxide In ethanol; water pH=7.5 - 9; Reagent/catalyst; Solvent; Temperature;	93%
Stage #1: tanshinone-IIA With sulfuric acid; acetic anhydride; acetic acid In dichloromethane at 25℃; for 0.0666667h; Stage #2: With sodium chloride In dichloromethane; water; Petroleum ether for 0.0833333h; Temperature;	72.6%
Stage #1: tanshinone-IIA With sulfuric acid; acetic anhydride; acetic acid at 25℃; Stage #2: With sodium chloride In water Product distribution / selectivity;
Stage #1: tanshinone-IIA With sulfuric acid; acetic anhydride; acetic acid In dichloromethane Flow reactor; Heating; Stage #2: With sodium chloride

tanshinone IIA (568-72-9) + benzoic acid (65-85-0) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl benzoate (1392502-49-6)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	95%

tanshinone IIA (568-72-9) + methyl trifluoromethanesulfonate (333-27-7) → 10,11-Dimethoxy-1,6,6-trimethyl-6,7,8,9-tetrahydro-phenanthro[1,2-b]furan (120727-43-7)

Conditions	Yield
Stage #1: tanshinone-IIA In tetrahydrofuran at -30℃; for 0.0833333h; Stage #2: methyl trifluoromethanesulfonate In tetrahydrofuran for 0.5h;	95%

BOC-glycine (4530-20-5) + tanshinone IIA (568-72-9) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl 2-((tert-butoxycarbonyl)amino)acetate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	92%

tanshinone IIA (568-72-9) + p-Toluic acid (99-94-5) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl 4-methylbenzoate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	92%

tanshinone IIA (568-72-9) + propionic acid (802294-64-0) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl propionate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Reagent/catalyst; Solvent; Sealed tube; regioselective reaction;	91%

tanshinone IIA (568-72-9) + cyclopropanecarboxylic acid (1759-53-1) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl cyclopropanecarboxylate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	90%

tanshinone IIA (568-72-9) + 2-Methoxybenzoic acid (579-75-9) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl 2-methoxybenzoate (1392502-51-0)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	90%

tanshinone IIA (568-72-9) + acetic anhydride (108-24-7) → 10,11-Diacetoxy-1,6,6-trimethyl-6,7,8,9-tetrahydro-phenanthro[1,2-b]furan (98796-69-1)

Conditions	Yield
Stage #1: tanshinone-IIA With palladium 10% on activated carbon; hydrogen In tetrahydrofuran at 15 - 25℃; Stage #2: acetic anhydride With pyridine In tetrahydrofuran at 15 - 25℃; for 3h;	90%

formaldehyd (50-00-0) + 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate hydrochloride (1151904-84-5) + tanshinone IIA (568-72-9) → C29H29NO5S

Conditions	Yield
With zinc diacetate In dimethyl sulfoxide at 60℃; for 24h;	89%

formaldehyd (50-00-0) + diphenylmethylpiperazine (841-77-0) + tanshinone IIA (568-72-9) → C37H38N2O3

Conditions	Yield
With zinc diacetate; acetic acid In chloroform Reflux; Inert atmosphere;	89%

tanshinone IIA (568-72-9) + butyric acid (107-92-6) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl butyrate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	88%

tanshinone IIA (568-72-9) → 6,7,8,9-tetrahydro-1,6,6-trimethylfuronaphth<2,1-e>oxepine-10,12-dione (61077-78-9)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen; acetic acid In water; benzene at 25℃; for 8h;	86%
With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 1h;	21%

tanshinone IIA (568-72-9) + acetic acid (64-19-7) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl acetate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical at 120℃; for 24h; Sealed tube; regioselective reaction;	85%

tanshinone IIA (568-72-9) + aniline (62-53-3) → C25H19NO3

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In toluene at 120℃; for 48h; Sealed tube;	85%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In toluene at 120℃; for 48h;	85%

2-thiophenylcarboxylic acid (527-72-0) + tanshinone IIA (568-72-9) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl thiophene-2-carboxylate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	81%

indole (120-72-9) + tanshinone IIA (568-72-9) → C35H30N2O2

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile at 50℃; for 72h;	81%

glutaric anhydride, (108-55-4) + tanshinone IIA (568-72-9) → C24H24O5

Conditions	Yield
With dmap; iron In tetrahydrofuran for 6h; Reflux; Inert atmosphere;	81%

tanshinone IIA (568-72-9) → 2-bromo-10,11-dioxo-1,6,6-trimethyl-6,7,8,9,10,11-hexahydro-phenanthro[1,2-b]furan (120727-39-1)

Conditions	Yield
With bromine; acetic acid at 20℃; for 4h;	80%
With bromine In tetrachloromethane at 20℃; for 0.333333h;
With N-Bromosuccinimide; acetic acid at 20℃; for 6h;
With hydrogen bromide; bromine In dichloromethane at 20℃; for 0.5h; Darkness;

tanshinone IIA (568-72-9) + hexanoic acid (142-62-1) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl hexanoate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	80%

tanshinone IIA (568-72-9) + naphthalene-2-carboxylate (93-09-4) → 1,6,6-trimethyl-10,11-dioxo-6,7,8,9,10,11-hexahydrophenanthro[1,2-b]furan-9-yl 2-naphthoate

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 24h; Sealed tube; regioselective reaction;	80%

tanshinone IIA (568-72-9) + 4-bromo-aniline (106-40-1) → C25H18BrNO3

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In toluene at 120℃; for 48h;	80%

tanshinone IIA (568-72-9) + chloroacetic acid ethyl ester (105-39-5) → 1,6,6-trimethyl-6,7,8,9,10,11-hexahydro-10,11-dioxophenanthro[1,2-b]furan-2-acetic acid ethyl ester

Conditions	Yield
With zirconium(IV) chloride In dichloromethane Reflux;	79%

6-fluoro-1H-indole (399-51-9) + tanshinone IIA (568-72-9) → C35H28F2N2O2

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile at 50℃; for 72h;	79%

tanshinone IIA (568-72-9) + phenol (108-95-2) → C25H22O4

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 36h; Reagent/catalyst; Solvent; Sealed tube; regioselective reaction;	78%

tanshinone IIA (568-72-9) → 2,2-difluoro-3,3-dihydroxy-8,8-dimethyl-2,3,5,6,7,8-hexahydrophenanthrene-1,4-dione

Conditions	Yield
With Selectfluor In water; acetonitrile at 80℃; for 12h; Reagent/catalyst; Solvent; Sealed tube;	77%
With Selectfluor In water; acetonitrile at 80℃; for 12h;	77%

Upstream product

• 100-66-3 methoxybenzene 
• 171979-69-4 5,5-dimethyl-5,6,7,8-tetrahydronaphthalen-1-ol 
• 18238-29-4 6,6-dimethyl-1-vinylcyclohex-1-ene 
• 113297-21-5 4,5-dihydro-3-methylbenzo[1,2-b]furan-4,5-dione 
• 33214-70-9 1,1-dimethyl-5-methoxytetralin 
• 171979-72-9 3-((S)-1-((tert-butyldimethylsilyl)oxy)-2-propyl)-7,7-dimethyl-4-hydroxy-2-((triisopropylsilyl)oxy)-7,8,9,10-tetrahydrophenanthrene 
• 578-57-4 2-bromoanisole 
• 2270-59-9 1-bromo-4-methylpent-3-ene 
• 171979-71-8 1,1-dimethyl-5-tetralyl trifluoromethanesulfonate 
• 109664-02-0 5,6,7,8-tetrahydro-3-hydroxy-2-[(1R)-2-hydroxy-1-methylethyl]-8,8-dimethyl-1,4-phenanthrenedione 
• 171979-67-2 2-diazo-1-(5,5-dimethyl-5,6,7,8-tetrahydro-1-naphthyl)-1-ethanone 
• 171979-68-3 1-(5,5-dimethyl-5,6,7,8-tetrahydro-1-naphthyl)ethan-1-one 
• 171979-70-7 1-methoxy-2-(4-methylpent-3-en-1-yl)benzene 
• 17545-07-2 (+/-)-cryptotanshinone 

Downstream Products

• 1245606-77-2 C₄₆H₄₂O₇S 
• 1245606-79-4 C₄₅H₃₉ClO₆ 
• 1245606-85-2 C₄₅H₃₉ClO₆ 
• 1245606-80-7 C₄₅H₃₉NO₈ 
• 1245606-81-8 C₄₅H₃₉NO₈ 
• 1245606-82-9 C₄₈H₄₆O₉ 
• 913582-28-2 C₄₅H₄₀O₆ 
• 1245606-78-3 C₄₅H₄₀O₇ 
• 913582-33-9 C₄₆H₄₂O₇ 
• 1245606-76-1 C₄₆H₄₂O₈ 
• 1245606-83-0 C₄₅H₃₉ClO₆ 
• 1245606-84-1 C₄₅H₄₀O₈ 
• 18887-18-8 1-hydroxytanshinone IIA 
• 119963-50-7 1,6,6-trimethyl-6,7-dihydrophenanthro[1,2-b]furan-10,11-dione 

Relevant articles and documents

Total synthesis of tanshinone IIA

A novel synthetic route toward tanshinone IIA has been developed. Key steps involve a base mediated furan ring formation, and an acyloin condensation reaction to construct the ortho-quinone ring.

Site-selective Csp3-H aryloxylation of natural product Tanshinone IIA and its analogues

A novel catalyst-free Csp3-H aryloxylation approach allowing for rapid installation of a wide range of aryloxyl groups regioselectively at the C-4 position of Tanshinone IIA under simple and mild conditions was developed. This unique protocol exhibited atom-/step-economy, low cost, high efficiency and robust functional-group tolerance, which will greatly facilitate to diversify the A-ring of the bioactive natural product.

Atomatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone, (-)-Cryptotanshinone, Tanshinone IIA, and (+/-)-Royleanone

The application of a photochemical aromatic annulation strategy in highly efficient total syntheses of several diterpenoid quinones isolated from the traditional Chinese medicine Dan Chen is reported.The pivotal step in each synthesis involves the assembly of the key tricyclic intermediate via the application of a recently developed "second generation" photochemical aromatic annulation method for the construction of highly substituted aromatic systems.In the total synthesis of neocryptotanchinone, the synthesis of the requisite diazo ketone anulation substrate 7 was achieved using paladium-mediated coupling reactions and an intramolecular Friedel-Crafts cyclization to form key carbon-carbon bonds.The pivotal aromatic annulation reaction was then accomplished by irradiating a solution of the diazo ketone 7 and the readily availabe siloxyalkyne 6 in benzene at room temperature.The desired tricyclic phenol 16 was produced in 58-65percent yield and was then converted to (+)-neocryptotanshinone (1) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen.Cyclization to generate (-)-cryptotanshinone (2) was accomplished in high yield by brief exposure of 1 to an ethanolic solution of concentrated sulfuric acid, and dehydrogenation of 2 with DDQ furnished tanshinone IIA (3).As a further demonstration of the utility of the photochemical aromatic annulation strategy in the construction of angularly-fused diterpenes, the total synthesis of (+/-)-royleanone (4) was also investigated.Irradiation of a solution of the diazo ketone 18 and siloxyalkyne 25 produced the tricyclic intermediate 26, which was converted in two steps to royleanone by desilylation and oxidation.