[(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate

Base Information

• Chemical Name: [(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate
• CAS No.: 66575-29-9
• Molecular Formula: C22H34O7
• Molecular Weight: 410.508
• Hs Code.: 29329990
• NSC Number: 758629
• Mol file: 66575-29-9.mol

Synonyms:[(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate;SR-05000001871;COLEOFORSIN;Spectrum_000347;Spectrum2_000871;Spectrum3_002000;Spectrum4_000197;Spectrum5_001283;BSPBio_003600;KBioGR_000773;KBioSS_000827;DivK1c_000337;SPECTRUM1503804;SPBio_000941;SCHEMBL8234478;HMS501A19;KBio1_000337;KBio2_000827;KBio2_003395;KBio2_005963;KBio3_003045;NINDS_000337;HMS1922I06;HMS2093K05;Pharmakon1600-01503804;NSC758629;AKOS024286668;CCG-213199;NSC-758629;SDCCGMLS-0066660.P001;IDI1_000337;NCGC00177971-01;SBI-0051842.P002;AB00052373_02;SR-05000001871-1;SR-05000001871-2;BRD-A55416093-001-01-5;BRD-A55416093-001-03-1

Chemical Property of [(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate

Chemical Property:

• Appearance/Colour: Colorless crystalline solid
• Vapor Pressure: 5.56E-13mmHg at 25°C
• Melting Point: 282-232 °C
• Refractive Index: 1.551
• Boiling Point: 519.9 °C at 760 mmHg
• PKA: 11.00±0.70(Predicted)
• Flash Point: 171.8 °C
• PSA: 113.29000
• Density: 1.23 g/cm³
• LogP: 1.51990
• Storage Temp.: −20°C
• Solubility.: DMSO: 5 mg/mL stable at least 6 months at room temperature
• Water Solubility.: Soluble in ethanol, dimethylsulfoxide and chloroform. Insolule in water.
• XLogP3: 1
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 3
• Exact Mass: 410.23045342
• Heavy Atom Count: 29
• Complexity: 747

Purity/Quality:

99% ^*data from raw suppliers

Forskolin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 21
• Safety Statements: 22-36/37

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(=O)OC1C(C2C(CCC(C2(C3(C1(OC(CC3=O)(C)C=C)C)O)C)O)(C)C)O
• Isomeric SMILES: CC(=O)O[C@H]1[C@H](C2[C@]([C@H](CCC2(C)C)O)([C@@]3([C@@]1(O[C@@](CC3=O)(C)C=C)C)O)C)O
• Description: Forskolin (66575-29-9) is a widely used adenylate cyclase activator.1 Forskolin also is a positive inotropic agent, vasodilator and induces platelet activation among other activities.2-5
• Uses: Forskolin is a diterpene isolated from Coleus forskohlii, possessing vasodilating and cardiostimulatory properties. Forskolin resensitizes cell receptors by activating the enzyme adenylyl cyclase and increasing the intracellular levels of cAMP. adenylate cyclase activator, antiglaucoma, hypotensive, vasodilator Cyclic AMP (cAMP) is an important signal carrier necessary for the proper biological response of cells to hormones, neurotransmitters, and other extracellular signals Forskolin is a naturally occurring diterpene that is produced by the Indian Coleus plant (C. forskohlii). It directly activates adenylyl cyclase through its catalytic subunit and is commonly used to raise levels of cAMP in a wide variety of intact cells and tissue preparations. Forskolin binds to adenylyl cyclase in membranes from stably transfected Sf9 cells expressing type 1 adenylyl cyclase with an IC50 value of 41 nM and demonstrates an EC50 value of 0.5 μM in an activation assay assessing formation of cAMP from ATP. Forskolin also interacts with glucose transporters and certain ion channels and has been used for examining adenylyl cyclase expression, regulation, and G protein signaling.[Cayman Chemical] An adenylate cyclase activator and MAP kinase inhibitor In purification of adenylate cyclase.

Technology Process of [(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate

There total 122 articles about [(3R,4aR,5S,6S,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.0%

acetic anhydride (108-24-7) + (+/-)-desacetyl forskolin (64657-20-1,66428-84-0,114298-68-9,119618-16-5,132620-06-5,132620-08-7) → (±)-forskolin (66428-89-5,66575-29-9,112420-42-5,119618-17-6,132620-07-6,64657-11-0)

Guidance literature:

With pyridine; at 0 ℃; for 20h;

DOI:10.1002/anie.201706809

Reference yield:

dimethyl 2,2-dimethylglutarate (13051-32-6) → (±)-forskolin (66428-89-5,66575-29-9,112420-42-5,119618-17-6,132620-07-6,64657-11-0)

Guidance literature:

Multi-step reaction with 35 steps

3: tetrahydrofuran / 0.5 h / -78 °C

4: H₂, quinoline / Lindlar catalyst / benzene / 2 h / 25 °C

5: DMAP / CH₂Cl₂ / 2 h / Heating

6: 35 percent / Pd(PPh₃)4, Et₃N / tetrahydrofuran / 5 h / Heating

7: 25 percent / toluene / 5 h / 220 - 230 °C / in sealed tube

8: 90 percent / OsO₄, Me₃NO, pyridine / 2-methyl-propan-2-ol; H₂O / 18 h / Heating

9: 81 percent / SO₃-pyridine, Et₃N / 20 h / 20 °C

10: 85 percent / NaTeH / ethanol / 0.5 h / 23 °C

11: 87 percent / t-BuNH₃-BH₃ / methanol / 21 h / 23 °C

12: 95 percent / TsOH / benzene / 1 h / 23 °C

13: 94 percent / MCPBA / CH₂Cl₂ / 0.5 h / -25 °C

14: 68 percent / CaCO₃ / toluene / 70 h / Heating

15: 92 percent / LiOMe / tetrahydrofuran / 72 h / 23 °C

16: 89 percent / LiAlH₄ / diethyl ether / 1 h / Heating

17: 90 percent / DMAP / 1,2-dichloro-ethane / 6 h / Heating

18: 83 percent / 1.) OsO₄, 2.) H₂S / 1.) pyridine, 20 deg C, 30 h, 2.) chloroform - dioxane, 23 deg C, 0.5 h

19: 91 percent / NaH / hexamethylphosphoric acid triamide; tetrahydrofuran / 3 h / 23 °C

20: 95 percent / TsOH / CHCl₃; methanol / 0.67 h / 20 °C

21: 96 percent / pyridine / 2 h / 20 °C

22: 95 percent / TsOH / 0.25 h / 20 °C

23: 95 percent / LiAlH₄ / diethyl ether / 0.17 h / 0 °C

24: 78 percent / SO₃-pyridine, Et₃N / dimethylsulfoxide / 16 h / 23 °C

25: 80 percent / tetrahydrofuran / 2 h / -78 - 20 °C

26: 79 percent / MnO₂ / benzene / 3 h / 23 °C

27: 93 percent / diethyl ether / 0.25 h / -78 °C

28: 95 percent / 1.) 3 N HCl - THF, 23 deg C, 1 h, then 0.2 N KOH - THF - MeOH, 23 deg C, 20 min

29: 78 percent / 1.) PhSeCl, 2.) Ra-Ni(W-2) / 1.) CH₂Cl₂, 0 deg C, 38 h, 2.) EtOH, reflux, 5 min

30: 97 percent / n-Bu₄NF / tetrahydrofuran / 5 h / 23 °C

31: 89 percent / n-Bu₃P / tetrahydrofuran / 0.5 h / 23 °C

32: 84 percent / 30percent H₂O₂ / CH₂Cl₂ / 20 h / 18 °C

33: 96 percent / 1.) DDQ, 2.) K₂CO₃ / 1.) CH₂Cl₂ - H₂O, 23 deg C, 48 h, 2.) MeOH, 23 deg C, 40 min

34: 77 percent / aq. HClO₄; tetrahydrofuran / 60 h / 23 °C

35: 85 percent / pyridine / 9 h / 0 °C

With pyridine; quinoline; dmap; manganese(IV) oxide; osmium(VIII) oxide; lithium aluminium tetrahydride; tetrakis(triphenylphosphine) palladium⁽⁰⁾; Phenylselenyl chloride; sodium hydrogen telluride; pyridine-SO₃ complex; trimethylamine-N-oxide; tributylphosphine; Ra-Ni(W-2); N-tert-butylaminoborane; hydrogen sulfide; lithium methanolate; tetrabutyl ammonium fluoride; hydrogen; dihydrogen peroxide; sodium hydride; potassium carbonate; triethylamine; 3-chloro-benzenecarboperoxoic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; calcium carbonate; Lindlar's catalyst; toluene-4-sulfonic acid; In tetrahydrofuran; pyridine; methanol; N,N,N,N,N,N-hexamethylphosphoric triamide; perchloric acid; diethyl ether; ethanol; dichloromethane; chloroform; water; dimethyl sulfoxide; 1,2-dichloro-ethane; toluene; tert-butyl alcohol; benzene;

DOI:10.1021/ja00219a058

Reference yield:

4,4-dimethyl-5-(tetrahydro-2H-pyran-2-yloxy)pentanal (141424-11-5) → (±)-forskolin (66428-89-5,66575-29-9,112420-42-5,119618-17-6,132620-07-6,64657-11-0)

Guidance literature:

Multi-step reaction with 34 steps

2: tetrahydrofuran / 0.5 h / -78 °C

3: H₂, quinoline / Lindlar catalyst / benzene / 2 h / 25 °C

4: DMAP / CH₂Cl₂ / 2 h / Heating

5: 35 percent / Pd(PPh₃)4, Et₃N / tetrahydrofuran / 5 h / Heating

6: 25 percent / toluene / 5 h / 220 - 230 °C / in sealed tube

7: 90 percent / OsO₄, Me₃NO, pyridine / 2-methyl-propan-2-ol; H₂O / 18 h / Heating

8: 81 percent / SO₃-pyridine, Et₃N / 20 h / 20 °C

9: 85 percent / NaTeH / ethanol / 0.5 h / 23 °C

10: 87 percent / t-BuNH₃-BH₃ / methanol / 21 h / 23 °C

11: 95 percent / TsOH / benzene / 1 h / 23 °C

12: 94 percent / MCPBA / CH₂Cl₂ / 0.5 h / -25 °C

13: 68 percent / CaCO₃ / toluene / 70 h / Heating

14: 92 percent / LiOMe / tetrahydrofuran / 72 h / 23 °C

15: 89 percent / LiAlH₄ / diethyl ether / 1 h / Heating

16: 90 percent / DMAP / 1,2-dichloro-ethane / 6 h / Heating

17: 83 percent / 1.) OsO₄, 2.) H₂S / 1.) pyridine, 20 deg C, 30 h, 2.) chloroform - dioxane, 23 deg C, 0.5 h

18: 91 percent / NaH / hexamethylphosphoric acid triamide; tetrahydrofuran / 3 h / 23 °C

19: 95 percent / TsOH / CHCl₃; methanol / 0.67 h / 20 °C

20: 96 percent / pyridine / 2 h / 20 °C

21: 95 percent / TsOH / 0.25 h / 20 °C

22: 95 percent / LiAlH₄ / diethyl ether / 0.17 h / 0 °C

23: 78 percent / SO₃-pyridine, Et₃N / dimethylsulfoxide / 16 h / 23 °C

24: 80 percent / tetrahydrofuran / 2 h / -78 - 20 °C

25: 79 percent / MnO₂ / benzene / 3 h / 23 °C

26: 93 percent / diethyl ether / 0.25 h / -78 °C

27: 95 percent / 1.) 3 N HCl - THF, 23 deg C, 1 h, then 0.2 N KOH - THF - MeOH, 23 deg C, 20 min

28: 78 percent / 1.) PhSeCl, 2.) Ra-Ni(W-2) / 1.) CH₂Cl₂, 0 deg C, 38 h, 2.) EtOH, reflux, 5 min

29: 97 percent / n-Bu₄NF / tetrahydrofuran / 5 h / 23 °C

30: 89 percent / n-Bu₃P / tetrahydrofuran / 0.5 h / 23 °C

31: 84 percent / 30percent H₂O₂ / CH₂Cl₂ / 20 h / 18 °C

32: 96 percent / 1.) DDQ, 2.) K₂CO₃ / 1.) CH₂Cl₂ - H₂O, 23 deg C, 48 h, 2.) MeOH, 23 deg C, 40 min

33: 77 percent / aq. HClO₄; tetrahydrofuran / 60 h / 23 °C

34: 85 percent / pyridine / 9 h / 0 °C

With pyridine; quinoline; dmap; manganese(IV) oxide; osmium(VIII) oxide; lithium aluminium tetrahydride; tetrakis(triphenylphosphine) palladium⁽⁰⁾; Phenylselenyl chloride; sodium hydrogen telluride; pyridine-SO₃ complex; trimethylamine-N-oxide; tributylphosphine; Ra-Ni(W-2); N-tert-butylaminoborane; hydrogen sulfide; lithium methanolate; tetrabutyl ammonium fluoride; hydrogen; dihydrogen peroxide; sodium hydride; potassium carbonate; triethylamine; 3-chloro-benzenecarboperoxoic acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; calcium carbonate; Lindlar's catalyst; toluene-4-sulfonic acid; In tetrahydrofuran; pyridine; methanol; N,N,N,N,N,N-hexamethylphosphoric triamide; perchloric acid; diethyl ether; ethanol; dichloromethane; chloroform; water; dimethyl sulfoxide; 1,2-dichloro-ethane; toluene; tert-butyl alcohol; benzene;

DOI:10.1021/ja00219a058

upstream raw materials:

(13R)-Spiroforskolin

7-deacetyl forskolin

acetyl chloride

acetic anhydride

Downstream raw materials:

forskolin 14,15-epoxide

15-<(m-chlorobenzoyl)oxy>-14-hydroxyforskolin

1β-Benzoyloxy-1-deoxycoleonol

coleonol-B

Refernces

• 1、 Hylse, Ond?ej,Maier, Luká?,Ku?era, Roman,Pere?ko, Tomá?,Svobodová, Aneta,Kubala, Luká?,Paruch, Kamil,?venda, Jakub. "A Concise Synthesis of Forskolin". supporting information. p. 12586 - 12589. Retrieved 2017/09/12.
• 2、 Hagiwara, Hisahiro,Takeuchi, Fumihide,Kudou, Masaru,Hoshi, Takashi,Suzuki, Toshio,Hashimoto, Toshihiro,Asakawa, Yoshinori. "Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin". . p. 4619 - 4624. Retrieved 2007/10/03.