20350-15-6

Basic information

• Product Name: Brefeldin A
• Synonyms: NECTROLIDE;SYNERGISIDIN;4h-cyclopent(f)oxacyclotridecin-4-one,1,6,7,8,9,11a-beta,12,13,14,14a-alpha-de;cahydro-1-beta-13-alpha-dihydroxy-6-beta-methyl-;cyanaein;CYANEIN;DECUMBIN;GAMMA-4-DIHDYROXY-2-(6-HYDROXY-1-HEPTENYL)-4-CYCLOPENTANECROTONIC ACID LAMBDA-LACTONE
• CAS NO: 20350-15-6
• Molecular Formula: C₁₆H₂₄O₄
• Molecular Weight: 280.36
• EINECS: 247-104-4
• Product Categories: All Inhibitors;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Signalling;antibiotic
• Mol File: 20350-15-6.mol
• Article Data: 28

Chemical Properties

• Melting Point: 200-205 °C
• Boiling Point: 492.7 °C at 760 mmHg
• Flash Point: 87 °C
• Appearance: White to almost white/Crystalline Powder
• Density: 1.108 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.513
• Storage Temp.: 2-8°C
• Solubility: methanol: 10 mg/mL, clear, colorless to faintly yellow
• PKA: 12.92±0.60(Predicted)
• Water Solubility: Soluble in dimethylsulfoxide, dichloromethane and ethanol. Slightly soluble in water.
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• Merck: 13,1355
• BRN: 25191
• CAS DataBase Reference: Brefeldin A(CAS DataBase Reference)
• NIST Chemistry Reference: Brefeldin A(20350-15-6)
• EPA Substance Registry System: Brefeldin A(20350-15-6)

Safety Data

• Hazard Codes: Xn,T
• Statements: 22-25-36/37/38-20/21/22
• Safety Statements: 24/25-45-36-26
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: GY8410000
• Hazardous Substances Data: 20350-15-6(Hazardous Substances Data)

Usage

Description

Brefeldin A, a macrolide isolated from Penicillium brefeldianum, is a potent inhibitor of cell growth with a wide range of bioactivity, including antiviral, antibiotic, antifungal, antitumor, and herbicidal properties. It specifically and reversibly blocks the translocation of proteins from the endoplasmic reticulum (ER) to the Golgi apparatus, causing disassembly of the Golgi complex and ER swelling in various mammalian cell lines. Brefeldin A also activates sphingomyelin metabolism and induces apoptosis.

Uses

Used in Pharmaceutical Industry:
Brefeldin A is used as an antibiotic, antiviral, antifungal, and antitumor agent due to its broad range of bioactivity. It modulates various cellular processes, making it a valuable tool in the development of therapeutics for various diseases.
Used in Research and Development:
Brefeldin A is used as a research tool to study intracellular transport by vesicles or endosomes, as it reversibly interferes with protein trafficking and secretion mediated by the Golgi apparatus and endoplasmic reticulum. It is also used to study endosomal trafficking and function in cells of plants, fungi, invertebrates, and vertebrates.
Used in Drug Delivery Systems:
Brefeldin A can be employed in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles can be used as carriers for Brefeldin A delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Used in Chemical Synthesis:
Brefeldin A, as a metabolite from Penicillium brefeldianum, can be used in chemical synthesis for the development of new compounds with potential applications in various industries, including pharmaceuticals and agriculture.

Biological Activity

Reversible inhibitor of protein translocation from the endoplasmic reticulum (ER) to the Golgi apparatus. Blocks binding of ADP-ribosylation factor to the Golgi apparatus and inhibits GDP-GTP exchange.

Biochem/physiol Actions

Primary TargetBlocks translocation of proteins from the endoplasmic reticulum (ER) to the Golgi apparatus

Purification Methods

Brefeldin A was isolated from Penicillium brefeldianum and recrystallised from aqueous MeOH/EtOAc or MeOH. Its solubility in H2O is 0.6mg/mL, 10mg/mL in MeOH and 24.9mg/mL in EtOH. The O-acetate recrystallises from Et2O/pentane and has m 130-131o, [] D +17o (c 0.95, MeOH). [Sigg Helv Chim Acta 47 1401 1964, UV and IR: H.rri et al. Helv Chim Acta 46 1235 1963, total synthesis: Kitahara et al. Tetrahedron 3021 1979, X-ray : Weber et al. Helv Chim Acta 54 2763 1971, Beilstein 18 III/IV 1220.]

References

1) Fujiwara et al. (1988) Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum; J. Biol. Chem., 263 18545 2) Shao et al. (1996), Brefeldin A is a potent inducer of apoptosis in human cancer cells independently of p53; Exp. Cell Res., 227 190 3) Linardic et al. (1996), Brefeldin A promotes hydrolysis of sphingomyelin; Cell Growth Differ., 7 765

InChI:InChI=1/C16H24O4/c1-11-5-3-2-4-6-12-9-13(17)10-14(12)15(18)7-8-16(19)20-11/h4,6-8,11-15,17-18H,2-3,5,9-10H2,1H3/b6-4-,8-7-/t11-,12-,13-,14+,15+/m0/s1

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Relevant articles and documents

A trans-vinylogous ester anion equivalent and its application to the synthesis of (+)-brefeldin A

A new trans-vinylogous ester anion equivalent which reacts with a variety of carbonyl systems has been developed. In addition, the concise total synthesis of (+)-brefeldin A utilizing facile acylation of this new variant of vinylogous acyl anion equivalent has been accomplished.

Application of Ru(II)-Catalyzed Enyne Cyclization in the Synthesis of Brefeldin A

The approach to brefeldin A described herein hinges on Ru(II)-catalyzed cycloisomerization of an enyne obtained by the reaction of an alkynylzinc reagent with an α-chloro sulfide. Other key steps include Mislow-Evans rearrangement, cross-metathesis, and macrocyclization using a Roush-Masamune protocol.

Synthesis and cytotoxic evaluation of acylated brefeldin a derivatives as potential anticancer agents

Brefeldin A has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on brefeldin A were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of brefeldin A under mild conditions and the preparation of a series of monoacylated and diacylated brefeldin A derivatives. Their cytotoxicity, antitumor activity against TE-1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. Brefeldin A 7-O-benzoate, brefeldin A 4,7-O-dibenzoate, and brefeldin A 7-O-biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50 μm, respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anticancer agents from brefeldin A derivatives.

Synthesis of (+)-Brefeldin-A

Two routes to (+)-brefeldin A have been investigated.In one the bicyclic ketone 2 was transformed into the hydroxy lactone 7.Subsequent reduction, opening of the heterocyclic ring and epimerization furnished the aldehyde 13.Further steps towards the natural product from this late stage intermediate 13 were not investigated.In the second route, the readily available hydroxy lactone 17 was converted into the enone 22.Conjugate addition of the requisite cuprate reagent to this afforded the 3,4-disubstituted cyclopentanone 24 which was converted into brefeldin-A 29 in five steps.

Trans-hydrogenation: Application to a concise and scalable synthesis of brefeldin a

The important biochemical probe molecule brefeldin A (1) has served as an inspirational target in the past, but none of the many routes has actually delivered more than just a few milligrams of product, where documented. The approach described herein is clearly more efficient; it hinges upon the first implementation of ruthenium-catalyzed trans-hydrogenation in natural products total synthesis. Because this unorthodox reaction is selective for the triple bond and does not touch the transannular alkene or the lactone site of the cycloalkyne, it outperforms the classical Birch-type reduction that could not be applied at such a late stage. Other key steps en route to 1 comprise an iron-catalyzed reductive formation of a non-terminal alkyne, an asymmetric propiolate carbonyl addition mediated by a bulky amino alcohol, and a macrocyclization by ring-closing alkyne metathesis catalyzed by a molybdenum alkylidyne.