Verruculogen

Base Information

• Chemical Name: Verruculogen
• CAS No.: 12771-72-1
• Molecular Formula: C₂₇H₃₃N₃O₇
• Molecular Weight: 511.575
• Hs Code.: 38220090
• European Community (EC) Number: 634-189-1
• ChEMBL ID: CHEMBL551369
• DSSTox Substance ID: DTXSID30894030
• Metabolomics Workbench ID: 66105
• Nikkaji Number: J1.270.297C,J228.044B
• Wikidata: Q78086174
• Wikipedia: Verruculogen
• Mol file: 12771-72-1.mol

Synonyms:verruculogen

Chemical Property of Verruculogen

Chemical Property:

• Appearance/Colour: White Powder
• Vapor Pressure: 6.85E-23mmHg at 25°C
• Melting Point: 233oC
• Refractive Index: 1.691
• Boiling Point: 688.43 °C at 760 mmHg
• Flash Point: 370.149 °C
• PSA: 112.01000
• Density: 1.424 g/cm³
• LogP: 1.59590
• Storage Temp.: 2-8°C
• Solubility.: Soluble in ethanol;Soluble in methanol;Soluble in DMSO;Soluble in dimethyl formamide
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 2
• Exact Mass: 511.23185040
• Heavy Atom Count: 37
• Complexity: 999

Purity/Quality:

98%Min ^*data from raw suppliers

Verruculogen ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T,Xn,F
• Statements: 23/24/25-36-20/21/22-11
• Safety Statements: 36/37/39-45-36/37-26-16

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(=CC1N2C3=C(C=CC(=C3)OC)C4=C2C(CC(OO1)(C)C)N5C(=O)C6CCCN6C(=O)C5(C4O)O)C
• Isomeric SMILES: CC(=C[C@@H]1N2C3=C(C=CC(=C3)OC)C4=C2[C@H](CC(OO1)(C)C)N5C(=O)[C@@H]6CCCN6C(=O)[C@@]5([C@H]4O)O)C
• Uses: Verruculogen is a tremorgenic mycotoxin, first isolated from Penicillium verruculosum in 1972. The structure was resolved as an indole alkaloid in 1974. Verruculogen is produced by several species of Penicillium and Aspergillus and its presence is a useful taxonomic phenotypic marker. The tremorgenic action of verruculogen is associated with increases in spontaneous glutamate and aspartate release, decreases in GABA levels and, at toxic doses, an increase in the number and decrease in the affinity of DHP receptors in rat cortex. In in vitro guinea pig ileum preparations, verruculogen causes an increase in contractile responses due to electrical field stimulation, attributed to enhancement of acetylcholine from presynaptic nerve terminals. Verruculogen also inhibits Ca2+-activated K+ channels, and is a cell cycle inhibitor blocking division at the M phase. Verruculogen is a tremorgenic mycotoxin isolated from species of Penicillium, Aspergillus, and other fungi. It selectively inhibits the activation of Maxi-K potassium channels by charybdotoxin with a K1/2 value of 170 nM. Verruculogen also promotes the release of excitatory neurotransmitters when injected directly into the brain of rats and, at high doses, arrests mouse mammary carcinoma cells in M phase of the cell cycle (MIC = 12.2 μM).[Cayman Chemical] Suggested starting dilutions are as follows: ICC/IF: 1:100-1:1000, IHC-P: 1:100-1:1000, WB: 1:500-1:3000. Not yet tested in other applications. Optimal working dilutions should be determined experimentally by the end user.

Technology Process of Verruculogen

There total 22 articles about Verruculogen 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:

3,3-dimethyl acrylaldehyde (107-86-8) + C22H27N3O7 → verruculogen (12771-72-1)

Guidance literature:

With boron trifluoride diethyl etherate; In 1,2-dichloro-ethane; at -20 ℃; for 0.25h; Inert atmosphere; Molecular sieve;

DOI:10.1021/jacs.5b07154

Reference yield:

fumitremorgin B (111139-38-9,12626-17-4) → verruculogen (12771-72-1)

Guidance literature:

With α-ketoglutaric acid; FtmOx₁ dioxygenase from Aspergillus fumigatus; oxygen; catalase; ascorbic acid; at 37 ℃; for 16h; pH=7.5; Tris-HCl buffer; Enzymatic reaction;

DOI:10.1039/b908392h

Reference yield:

methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(1H-indol-3-yl)propanoate (141215-69-2,33900-28-6) → verruculogen (12771-72-1)

Guidance literature:

Multi-step reaction with 12 steps

1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere

1.2: 1 h / -78 - 23 °C / Inert atmosphere

2.1: (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 1,10-Phenanthroline; bis(pinacol)diborane; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane / hexane / 24 h / 80 °C / Inert atmosphere; Sealed tube

2.2: 36 h / 23 °C / Inert atmosphere; Sealed tube

3.1: hydrogenchloride / water; ethyl acetate / 3 h / 60 °C / Inert atmosphere

4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 23 °C / Inert atmosphere

5.1: chloroform / 1 h / 0 °C / Inert atmosphere; Molecular sieve

6.1: trifluoroacetic acid / 24 h / 0 °C / Inert atmosphere

7.1: sodium hydrogencarbonate / dichloromethane; water / 5 h / 23 °C / Inert atmosphere

8.1: Nitrosobenzene; zirconium(IV) chloride / dichloromethane / 3 h / 0 - 23 °C / Inert atmosphere

9.1: diethylamine / tetrahydrofuran / 40 °C / Inert atmosphere

10.1: osmium(VIII) oxide; 4-methyl-morpholine / water; acetonitrile; tert-butyl alcohol; acetone / 8 h / 23 °C / Inert atmosphere

11.1: tetrabutyl ammonium fluoride; acetic acid / tetrahydrofuran; N,N-dimethyl-formamide / 0.17 h / 0 °C / Inert atmosphere

12.1: boron trifluoride diethyl etherate / 1,2-dichloro-ethane / 0.25 h / -20 °C / Inert atmosphere; Molecular sieve

With 4-methyl-morpholine; hydrogenchloride; osmium(VIII) oxide; 1,10-Phenanthroline; (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; boron trifluoride diethyl etherate; tetrabutyl ammonium fluoride; zirconium(IV) chloride; sodium hydrogencarbonate; acetic acid; diethylamine; Nitrosobenzene; trifluoroacetic acid; bis(pinacol)diborane; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane; lithium hexamethyldisilazane; In tetrahydrofuran; hexane; dichloromethane; chloroform; water; ethyl acetate; 1,2-dichloro-ethane; N,N-dimethyl-formamide; acetone; acetonitrile; tert-butyl alcohol; 5.1: |Pictet-Spengler Synthesis / 6.1: |Pictet-Spengler Synthesis;

DOI:10.1021/jacs.5b07154

upstream raw materials:

Fumitremorgin A

fumitremorgin B

methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(1H-indol-3-yl)propanoate

3,3-dimethyl acrylaldehyde

Downstream raw materials:

Fumitremorgin A

Refernces

• 1、 Feng, Yu,Holte, Dane,Zoller, Jochen,Umemiya, Shigenobu,Simke, Leah R.,Baran, Phil S.. "Total synthesis of verruculogen and fumitremorgin a enabled by ligand-controlled C-H borylation". . p. 10160 - 10163. Retrieved 2015/09/01.
• 2、 Steffan, Nicola,Grundmann, Alexander,Afiyatullov, Shamil,Ruan, Hanli,Li, Shu-Ming. "FtmOx1, a non-heme Fe(ii) and α-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus". supporting information; experimental part. p. 4082 - 4087. Retrieved 2009/12/06.