Gliotoxin

Base Information

• Chemical Name: Gliotoxin
• CAS No.: 67-99-2
• Molecular Formula: C13H14 N2 O4 S2
• Molecular Weight: 326.397
• Hs Code.: 29419090
• European Community (EC) Number: 636-170-3
• UNII: 5L648PH06K
• DSSTox Substance ID: DTXSID60877179
• Nikkaji Number: J9.768C
• Wikipedia: Gliotoxin
• Wikidata: Q413364
• NCI Thesaurus Code: C63680
• Pharos Ligand ID: 9JXF4NRLBJGV
• Metabolomics Workbench ID: 53184
• ChEMBL ID: CHEMBL331627
• Mol file: 67-99-2.mol

Synonyms:Aspergillin;Gliotoxin;Gliotoxins

Chemical Property of Gliotoxin

Chemical Property:

• Vapor Pressure: 1.22E-22mmHg at 25°C
• Melting Point: 221°C (rough estimate)
• Refractive Index: 1.6510 (estimate)
• Boiling Point: 699.7°C at 760 mmHg
• PKA: 12.90±0.40(Predicted)
• Flash Point: 377°C
• PSA: 131.68000
• Density: 1.74g/cm³
• LogP: -0.42790
• Storage Temp.: 2-8°C
• Solubility.: chloroform: 10 mg/mL, clear, colorless
• XLogP3: -0.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 1
• Exact Mass: 326.03949928
• Heavy Atom Count: 21
• Complexity: 621

Purity/Quality:

98%,99%, ^*data from raw suppliers

Gliotoxin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): 50675
• Hazard Codes: T,Xn,F
• Statements: 25-36-20/21/22-11
• Safety Statements: 36/37/39-45-36/37-16

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CN1C(=O)C23CC4=CC=CC(C4N2C(=O)C1(SS3)CO)O
• Isomeric SMILES: CN1C(=O)[C@]23CC4=CC=C[C@@H]([C@H]4N2C(=O)[C@]1(SS3)CO)O
• Description: Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains of Aspergillus and other fungi with diverse biological activities. It inhibits 20S proteasomal chymotrypsin activity (IC50 = 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB. Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils. It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively). Under reducing conditions, gliotoxin inhibits leukotriene A4 hydrolase (LTA4H; ) epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4 (LTB4; ) synthesis in neutrophils and monocytes. In vivo, gliotoxin (5 mg/kg) reduces LTB4 plasma levels and blocks peritoneal neutrophil infiltration in a mouse model of peritonitis induced by zymosan A . It also inhibits geranylgeranyltransferase I and farnesyltransferase (IC50s = 17 and 80 μM, respectively).
• Uses: Gliotoxin is a sulfur-containing mycotoxin produced by species of fungi and pathogens of humans. Gliotoxin exhibits inhibitory activities against histone H3K9 methyltransferase, a key enzyme in the re gulation of transcriptional activity by writing epigenetic marks. Gliotoxin also exhibits immunosuppressive properties by causing apoptosis of cells of the immune system. In addition, various studies suggests Gliotoxin may also be a potential anti-inflammatory, antibiotic, antifungal and antiviral agent. Gliotoxin is a potent epithiodioxopiperazine mycotoxin produced by species of Gliocladium, Aspergillus and Penicillium. At the cellular level gliotoxin inhibits a broad range of unrelated mechanisms, including inhibition of chymotrypsin-like activity of the 20S proteasome and Ca2+ release from mitochondria, activation of transcription factor NF-κB in response to a variety of stimuli in T and B cells, anti-inflammatory activity, and inhibition of farnesyltransferase and geranylgeranyltransferase. The mode of action appears to be via covalent interaction with proteins through mixed disulphide formation. Gliotoxin inhibits a number of thiol-requiring enzymes and also displays antioxidant and immunomodulatory activity.

Technology Process of Gliotoxin

There total 44 articles about Gliotoxin 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: 23.0%

desthiogliotoxin → gliotoxin G (53348-47-3) + gliotoxin (67-99-2)

Guidance literature:

With sulfur; lithium hexamethyldisilazane; In tetrahydrofuran; at 25 ℃; for 2.08333h; stereoselective reaction; Inert atmosphere;

DOI:10.1021/ja308429f

Reference yield:

(2S,3aR,7aR)-3a-Hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydro-indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (144534-57-6) → gliotoxin G (53348-47-3) + gliotoxin (67-99-2)

Guidance literature:

Multi-step reaction with 14 steps

1.1: sodium tetrahydroborate; cerium(III) chloride heptahydrate / methanol / 4 h / -20 - 0 °C / Inert atmosphere

2.1: dmap; triethylamine / dichloromethane / 1 h / 0 °C / Inert atmosphere

3.1: palladium diacetate; triethylamine; triphenylphosphine / toluene / 3.33 h / 25 - 110 °C / Inert atmosphere

4.1: oxygen; 5,15,10,20-tetraphenylporphyrin / dichloromethane / 24 h / 25 °C / Inert atmosphere; UV-irradiation

5.1: thiourea / methanol / 2 h / 25 °C / Inert atmosphere

6.1: triethylamine / dichloromethane / 1.5 h / 0 °C / Inert atmosphere

7.1: toluene / 3 h / 110 °C / Inert atmosphere

8.1: phosphorous acid trimethyl ester / 16 h / 111 °C / Inert atmosphere

9.1: hydrogenchloride / diethyl ether; dichloromethane / 0.25 h / 0 °C / Inert atmosphere

10.1: lithium hydroxide / tetrahydrofuran; water / 5 h / 0 - 25 °C

10.2: pH 3

11.1: 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 15 h / 0 - 25 °C / Inert atmosphere

12.1: dichloromethane / 3 h / 0 - 25 °C / Inert atmosphere

13.1: triethylamine / dichloromethane / 15 h / 0 - 25 °C / Inert atmosphere

14.1: sulfur; lithium hexamethyldisilazane / tetrahydrofuran / 2.08 h / 25 °C / Inert atmosphere

With hydrogenchloride; sulfur; dmap; sodium tetrahydroborate; 1-hydroxy-7-aza-benzotriazole; cerium(III) chloride heptahydrate; oxygen; palladium diacetate; 5,15,10,20-tetraphenylporphyrin; triethylamine; N-ethyl-N,N-diisopropylamine; thiourea; triphenylphosphine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; lithium hydroxide; lithium hexamethyldisilazane; phosphorous acid trimethyl ester; In tetrahydrofuran; methanol; diethyl ether; dichloromethane; water; toluene; 1.1: |Luche Cerium Reduction;

DOI:10.1021/ja308429f

Reference yield:

C15H23NO6 (1402592-61-3) → gliotoxin G (53348-47-3) + gliotoxin (67-99-2)

Guidance literature:

Multi-step reaction with 13 steps

1.1: dmap; triethylamine / dichloromethane / 1 h / 0 °C / Inert atmosphere

2.1: palladium diacetate; triethylamine; triphenylphosphine / toluene / 3.33 h / 25 - 110 °C / Inert atmosphere

3.1: oxygen; 5,15,10,20-tetraphenylporphyrin / dichloromethane / 24 h / 25 °C / Inert atmosphere; UV-irradiation

4.1: thiourea / methanol / 2 h / 25 °C / Inert atmosphere

5.1: triethylamine / dichloromethane / 1.5 h / 0 °C / Inert atmosphere

6.1: toluene / 3 h / 110 °C / Inert atmosphere

7.1: phosphorous acid trimethyl ester / 16 h / 111 °C / Inert atmosphere

8.1: hydrogenchloride / diethyl ether; dichloromethane / 0.25 h / 0 °C / Inert atmosphere

9.1: lithium hydroxide / tetrahydrofuran; water / 5 h / 0 - 25 °C

9.2: pH 3

10.1: 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 15 h / 0 - 25 °C / Inert atmosphere

11.1: dichloromethane / 3 h / 0 - 25 °C / Inert atmosphere

12.1: triethylamine / dichloromethane / 15 h / 0 - 25 °C / Inert atmosphere

13.1: sulfur; lithium hexamethyldisilazane / tetrahydrofuran / 2.08 h / 25 °C / Inert atmosphere

With hydrogenchloride; sulfur; dmap; 1-hydroxy-7-aza-benzotriazole; oxygen; palladium diacetate; 5,15,10,20-tetraphenylporphyrin; triethylamine; N-ethyl-N,N-diisopropylamine; thiourea; triphenylphosphine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; lithium hydroxide; lithium hexamethyldisilazane; phosphorous acid trimethyl ester; In tetrahydrofuran; methanol; diethyl ether; dichloromethane; water; toluene;

DOI:10.1021/ja308429f

upstream raw materials:

C₂₁H₂₂N₂O₅S₂

C₂₁H₂₂N₂O₅S₂

(2S,3aR,7aR)-3a-Hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydro-indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

C₁₅H₂₃NO₆

Downstream raw materials:

5a,6-didehydrogliotoxin

diacetylbisdethiobis(methylthio)gliotoxin

C₂₁H₂₂N₂O₅S₂

C₂₁H₂₂N₂O₅S₂

Refernces

• 1、 Bernardo, Paul H.,Chai, Christina L.L.,Deeble, Geoffrey J.,Liu, Xue-Ming,Waring, Paul. "Evidence for gliotoxin-glutathione conjugate adducts". . p. 483 - 485. Retrieved 2001.
• 2、 Nicolaou, K. C.,Lu, Min,Totokotsopoulos, Sotirios,Heretsch, Philipp,Giguere, Denis,Sun, Ya-Ping,Sarlah, David,Nguyen, Thu H.,Wolf, Ian C.,Smee, Donald F.,Day, Craig W.,Bopp, Selina,Winzeler, Elizabeth A.. "Synthesis and biological evaluation of epidithio-, epitetrathio-, and bis-(methylthio)diketopiperazines: Synthetic methodology, enantioselective total synthesis of epicoccin G, 8,8′-epi-ent-rostratin B, gliotoxin, gliotoxin G, emethallicin E, and haematocin and discovery of new antiviral and antimalarial agents". . p. 17320 - 17332,13. Retrieved 2020/09/02.