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

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

Uses

1. Anticancer Applications:
Tanshinone IIA is used as an antineoplastic agent, exhibiting potential inhibitory effects on tumor growth in vivo. It is particularly effective against various types of cancer cells, including A549 lung cancer cells and leukemia cells. It modulates several oncological signaling pathways and induces apoptosis in cancer cells, making it a promising candidate for cancer treatment.
2. Cardiovascular Applications:
Tanshinone IIA is used as a vasodilator, promoting blood circulation and maintaining vasodilating activity in vivo. This property makes it useful in treating cardiovascular diseases and improving blood flow.
3. Anti-inflammatory Applications:
Tanshinone IIA is used as an anti-inflammatory agent, inhibiting the production of various pro-inflammatory cytokines and mediators, such as TNF-α, IL-1β, IL-6, NO, INFγ, and the expression of iNOS and IL-12. It also blocks human aortic smooth muscle cell migration and inhibits MMP-9 activity, making it a potential therapeutic agent for inflammatory diseases.
4. Bone Resorption Inhibition:
Tanshinone IIA is used as a bone resorption inhibitor, potentially useful in the treatment of bone-related disorders and conditions, such as osteoporosis.
5. Antiproliferative Applications:
Tanshinone IIA is used as an antiproliferative agent, inhibiting the proliferation of various cancer cells and potentially useful in cancer therapy.
6. Apoptosis Induction:
Tanshinone IIA is used to induce apoptosis in cancer cells, promoting cell death and potentially enhancing the efficacy of cancer treatments.
Used in Pharmaceutical Industry:
Tanshinone IIA is used as an active pharmaceutical ingredient for the development of drugs targeting various diseases, including cancer, cardiovascular diseases, and inflammatory conditions.
Used in Traditional Chinese Medicine:
Tanshinone IIA is used as a key component in traditional Chinese medicine formulations, leveraging its diverse therapeutic properties for the treatment of various ailments and promoting overall health and well-being.

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.

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

• 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 
• 17545-07-2 (+/-)-cryptotanshinone 
• 171979-69-4 5,5-dimethyl-5,6,7,8-tetrahydronaphthalen-1-ol 
• 100-66-3 methoxybenzene 
• 171979-70-7 1-methoxy-2-(4-methylpent-3-en-1-yl)benzene 
• 171979-68-3 1-(5,5-dimethyl-5,6,7,8-tetrahydro-1-naphthyl)ethan-1-one 
• 171979-67-2 2-diazo-1-(5,5-dimethyl-5,6,7,8-tetrahydro-1-naphthyl)-1-ethanone 
• 171979-72-9 3-((S)-1-((tert-butyldimethylsilyl)oxy)-2-propyl)-7,7-dimethyl-4-hydroxy-2-((triisopropylsilyl)oxy)-7,8,9,10-tetrahydrophenanthrene 
• 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 
• 33214-70-9 1,1-dimethyl-5-methoxytetralin 
• 578-57-4 2-bromoanisole 
• 2270-59-9 1-bromo-4-methylpent-3-ene 

Downstream Products

• 790673-00-6 neosalvianen 
• 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 
• 1392502-63-4 C₂₆H₂₁FO₅ 

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.

Design, synthesis and biological evaluation of tanshinone IIA-based analogues: Potent inhibitors of microtubule formation and angiogenesis

We report the structural optimization of tanshinone IIA, a natural product which possesses anti-tumor properties but low water-solubility, weak antiproliferative activity and poor PK properties. A new series of ring A/C/D modified tanshinone analogues were synthesized and studied for their antiproliferative capacities against six human cancer cell lines. SAR study revealed that ring A cleavage of tanshinone IIA led to improved anti-cancer activity. Introduction of a methoxy group to the phenyl ring could enhance the anti-cancer activity even further. Compound 2f with methoxy group at C-8 position was selected as an early lead with IC50 values of 0.28–3.16 μM against six tested cell lines. 2f could bind to tubulin colchicine site, inhibit tubulin assembly and disrupt the normal formation of microtubule networks. Cellular mechanistic studies revealed that 2f induced apoptotic cell death of A549 cells in a dose-dependent manner. In vitro investigations showed that 2f impeded the tubule-formation of HUVECs and potently inhibited the proliferation, migration and invasion of A549 cells as well as HUVECs. Furthermore, the in vivo anti-angiogenic effect of 2f was confirmed via a zebrafish model test. The satisfactory physicochemical property and metabolic stability of 2f, as well as improved water-solubility, further suggested that 2f could serve as a promising tubulin inhibitor and anti-angiogenic agent.

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.

Facile and efficient total synthesis of (±)-cryptotanshinone and tanshinone IIA

A concise synthesis of (±)-cryptotanshinone and tanshinone IIA from readily available 1,5-naphthalenediol is described in which the key step is the radical cyclization process promoted by SmI2 to make a furan ring.

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.

Ultrasound-Promoted Cycloadditions in the Synthesis of Salvia miltiorrhiza Abietanoid o-Quinones

The ultrasound-promoted Diels-Alder reaction of 3-methyl-4,5-benzofurandione with appropriately substituted vinylcyclohexenes has led to the synthesis of tanshinone IIA, nortanshinone, tanshindiol B, methyl tanshinonate, and tanshinone IIB, biologically active metabolites of the Chinese traditional medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge.Methyltanshinquinone, the dihydro derivative of the natural product, methylenetanshinquinone, was similarly prepared.The effect of ultrasound in promoting the cycloadditions parallels that of high pressure and improved the regioselectivity in favour of the natural isomers.