Ophiobolin A

Base Information

• Chemical Name: Ophiobolin A
• CAS No.: 4611-05-6
• Deprecated CAS: 1347-57-5,5843-70-9,11022-22-3,17046-71-8
• Molecular Formula: C₂₅H₃₆O₄
• Molecular Weight: 400.558
• Hs Code.: 2932190090
• European Community (EC) Number: 636-934-6
• ChEMBL ID: CHEMBL522808
• DSSTox Substance ID: DTXSID301017596
• Metabolomics Workbench ID: 28700
• Nikkaji Number: J14.566A
• Wikidata: Q27107581
• Mol file: 4611-05-6.mol

Synonyms:ophiobolin A

Chemical Property of Ophiobolin A

Chemical Property:

• Vapor Pressure: 6.91E-14mmHg at 25°C
• Melting Point: 182°C
• Refractive Index: 1.4460 (estimate)
• Boiling Point: 539.4°Cat760mmHg
• PKA: 13.84±0.70(Predicted)
• Flash Point: 177.8°C
• PSA: 63.60000
• Density: 1.14g/cm³
• LogP: 4.40800
• Storage Temp.: 2-8°C
• Solubility.: Soluble in DMSO (up to 10 mg/ml)
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 400.26135963
• Heavy Atom Count: 29
• Complexity: 778

Purity/Quality:

99% ^*data from raw suppliers

Ophiobolin A ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CC(OC12CCC3(C2CC=C(C4C(C3)C(CC4=O)(C)O)C=O)C)C=C(C)C
• Isomeric SMILES: C[C@H]1C[C@@H](O[C@@]12CC[C@]3([C@H]2C/C=C(\[C@@H]4[C@H](C3)[C@](CC4=O)(C)O)/C=O)C)C=C(C)C
• Description: Ophiobolin A (4611-05-6) selectively inhibits the growth of cancer cells (IC50=0.4-4.3 μM) over normal cells (IC50=20.9 μM).1 Induces non-apoptotic cell death in glioblastoma cells and is active in an in vivo model.2 Covalently reacts with primary amines such as lysine side chains2 and phosphatidylethanolamine3 forming unique pyrrole adducts. Induces ER stress4, paraptosis4 and autophagy5.
• Uses: Ophiobolin A is the dominant member of a class of phytotoxic metabolites produced by plant pathogenic fungi. Ophiobolin A acts by inhibiting calmodulin action in calcium regulation.

Technology Process of Ophiobolin A

There total 51 articles about Ophiobolin A 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:

(5α,7E,18R)-14,18-epoxyophiobola-7,19-diene-3,5,25-triol → Ophiobolin A (4611-05-6,24034-72-8,90411-19-1)

Guidance literature:

(5α,7E,18R)-14,18-epoxyophiobola-7,19-diene-3,5,25-triol; With oxalyl dichloride; dimethyl sulfoxide; In dichloromethane; at -78 ℃; for 0.5h; Inert atmosphere;

With triethylamine; In dichloromethane; at -78 - 20 ℃; Inert atmosphere;

DOI:10.1002/anie.201104447

Reference yield:

2-[(2R,4S,5S,6R,7R)-7-[((1S,2S,3S)-2-tert-butyldimethylsilyloxymethyl-3-tert-butyldiphenylsilyloxy-5-oxocyclopentyl)methyl]-2-tert-butyldiphenylsilyloxymethyl-4,7-dimethyl-1-oxaspiro[4.4]non-6-yl]ethyl 2,2-dimethylpropanoate (1344673-78-4) → Ophiobolin A (4611-05-6,24034-72-8,90411-19-1)

Guidance literature:

Multi-step reaction with 23 steps

1.1: diethyl ether / 2.5 h / -78 - 0 °C / Inert atmosphere

2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

2.2: -78 - 20 °C / Inert atmosphere

3.1: potassium tert-butylate / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere

3.2: 0 °C / Inert atmosphere

4.1: pyridinium p-toluenesulfonate / ethanol / 20 °C / Inert atmosphere

5.1: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere

6.1: diethyl ether / 0 °C / Inert atmosphere

7.1: Dess-Martin periodane / dichloromethane / 20 °C / Inert atmosphere

8.1: 1H-imidazole / N,N-dimethyl-formamide / 20 °C / Inert atmosphere

9.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 0.5 h / -78 °C / Inert atmosphere

9.2: -78 °C / Inert atmosphere

10.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine / methanol; toluene / 50 °C / Inert atmosphere

11.1: diisobutylaluminium hydride / hexane / -78 °C / Inert atmosphere

12.1: pyridine; dmap / dichloromethane / 20 °C / Inert atmosphere

13.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Inert atmosphere

14.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C / Inert atmosphere

15.1: sodium hydride / N,N-dimethyl-formamide / 0 °C / Inert atmosphere

16.1: diisobutylaluminium hydride / hexane / -78 °C / Inert atmosphere

17.1: Hoveyda-Grubbs catalyst second generation; p-benzoquinone / toluene / 110 °C / Inert atmosphere

18.1: sodium hydride / N,N-dimethyl-formamide / 0 °C / Inert atmosphere

19.1: pyridinium p-toluenesulfonate / ethanol / 20 °C / Inert atmosphere

20.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

20.2: -78 - 20 °C / Inert atmosphere

21.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere

21.2: 20 °C / Inert atmosphere

22.1: naphthalene; lithium / tetrahydrofuran / -30 °C / Inert atmosphere

23.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

23.2: -78 - 20 °C / Inert atmosphere

With pyridine; 1H-imidazole; dmap; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; Hoveyda-Grubbs catalyst second generation; oxalyl dichloride; naphthalene; potassium tert-butylate; tetrabutyl ammonium fluoride; pyridinium p-toluenesulfonate; lithium; potassium hexamethylsilazane; sodium hydride; diisobutylaluminium hydride; Dess-Martin periodane; dimethyl sulfoxide; triethylamine; N-ethyl-N,N-diisopropylamine; p-benzoquinone; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In tetrahydrofuran; methanol; diethyl ether; ethanol; hexane; dichloromethane; dimethyl sulfoxide; N,N-dimethyl-formamide; toluene; 2.1: Swern oxidation / 2.2: Swern oxidation / 3.1: Wittig reaction / 3.2: Wittig reaction / 20.1: Swern oxidation / 20.2: Swern oxidation / 21.1: Wittig reaction / 21.2: Wittig reaction / 23.1: Swern oxidation / 23.2: Swern oxidation;

DOI:10.1002/anie.201104447

Reference yield:

(1R,2S,3S,4S)-3-tert-butyldimethylsilyloxymethyl-4-tert-butyldiphenylsilyloxy-2-{[(2R,4S,5S,6R,7R)-2-tert-butyldiphenylsilyloxymethyl-6-(2-hydroxyethyl)-4,7-dimethyl-1-oxaspiro[4.4]non-7-yl]methyl}-1-methylcyclopentanol (1344673-92-2) → Ophiobolin A (4611-05-6,24034-72-8,90411-19-1)

Guidance literature:

Multi-step reaction with 22 steps

1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

1.2: -78 - 20 °C / Inert atmosphere

2.1: potassium tert-butylate / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere

2.2: 0 °C / Inert atmosphere

3.1: pyridinium p-toluenesulfonate / ethanol / 20 °C / Inert atmosphere

4.1: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere

5.1: diethyl ether / 0 °C / Inert atmosphere

6.1: Dess-Martin periodane / dichloromethane / 20 °C / Inert atmosphere

7.1: 1H-imidazole / N,N-dimethyl-formamide / 20 °C / Inert atmosphere

8.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 0.5 h / -78 °C / Inert atmosphere

8.2: -78 °C / Inert atmosphere

9.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine / methanol; toluene / 50 °C / Inert atmosphere

10.1: diisobutylaluminium hydride / hexane / -78 °C / Inert atmosphere

11.1: pyridine; dmap / dichloromethane / 20 °C / Inert atmosphere

12.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Inert atmosphere

13.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C / Inert atmosphere

14.1: sodium hydride / N,N-dimethyl-formamide / 0 °C / Inert atmosphere

15.1: diisobutylaluminium hydride / hexane / -78 °C / Inert atmosphere

16.1: Hoveyda-Grubbs catalyst second generation; p-benzoquinone / toluene / 110 °C / Inert atmosphere

17.1: sodium hydride / N,N-dimethyl-formamide / 0 °C / Inert atmosphere

18.1: pyridinium p-toluenesulfonate / ethanol / 20 °C / Inert atmosphere

19.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

19.2: -78 - 20 °C / Inert atmosphere

20.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere

20.2: 20 °C / Inert atmosphere

21.1: naphthalene; lithium / tetrahydrofuran / -30 °C / Inert atmosphere

22.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere

22.2: -78 - 20 °C / Inert atmosphere

With pyridine; 1H-imidazole; dmap; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; Hoveyda-Grubbs catalyst second generation; oxalyl dichloride; naphthalene; potassium tert-butylate; tetrabutyl ammonium fluoride; pyridinium p-toluenesulfonate; lithium; potassium hexamethylsilazane; sodium hydride; diisobutylaluminium hydride; Dess-Martin periodane; dimethyl sulfoxide; triethylamine; N-ethyl-N,N-diisopropylamine; p-benzoquinone; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In tetrahydrofuran; methanol; diethyl ether; ethanol; hexane; dichloromethane; dimethyl sulfoxide; N,N-dimethyl-formamide; toluene; 1.1: Swern oxidation / 1.2: Swern oxidation / 2.1: Wittig reaction / 2.2: Wittig reaction / 19.1: Swern oxidation / 19.2: Swern oxidation / 20.1: Wittig reaction / 20.2: Wittig reaction / 22.1: Swern oxidation / 22.2: Swern oxidation;

DOI:10.1002/anie.201104447

upstream raw materials:

(-)-tert-butyl-[(2R,4S,5S,6R,7S)-7-methoxymethoxymethyl-4,7-dimethyl-6-vinyl-1-oxaspiro[4.4]non-2-ylmethoxy]diphenylsilane

2-[(2R,4S,5S,6R,7S)-2-{[(tert-butyldiphenylsilyl)oxy]methyl}-7-[(methoxymethoxy)methyl]-4,7-dimethyl-1-oxaspiro[4.4]nonan-6-yl]ethan-1-ol

(2R,3S,4S)-2-bromo-3-(tert-butyldimethylsilyl)oxymethyl-4-tert-butyldiphenylsilyloxycyclopentanone

(2S,3S,4S)-2-bromo-3-tert-butyldimethylsilyloxymethyl-4-tert-butyldiphenylsilyloxycyclopentanone

Refernces

• 1、 Tsuna, Kazuhiro,Noguchi, Naoyoshi,Nakada, Masahisa. "Convergent total synthesis of (+)-ophiobolin A". . p. 9452 - 9455. Retrieved 2011/11/06.