PHORBOL

Description

Phorbol is a diterpene originally isolated from croton oil. It is used as a starting material for the semisynthesis of various phorbol diesters, which are structurally analogous to diacylglycerol and activate PKC isoforms by associating with their C1 domains.

Description

(+)-Phorbol is a long-known, structurally complex natural product. In 1934, Swiss chemists Bonifaz Flaschentr?ger and Rudolf von Wolffersdorff isolated it from hydrolyzed croton oil, which was a known tumor-promoting substance. Research teams led by E. Hecker in Germany and George Ferguson in Britain reported its structure in 1967.
According to the?Merck Index, “Phorbol has a structural skeleton based on cyclopropabenzazulene.” It also has a daunting eight stereogenic centers. Three research groups have published total syntheses of phorbol, but the first two produced the racemic compound. Just this year, Phil S. Baran and colleagues at the Scripps Research Institute (La Jolla, CA) and LEO Pharma (Ballerup, Denmark) found a way?to make phorbol enantioselectively?in 19 steps, less than half the number required in earlier work.
Baran’s group’s work and future, more efficient syntheses should provide sufficient quantities of phorbol and its esters for potential drug development. In addition to their ability to promote rapid tumor growth, phorbol derivatives may be useful immunotherapy, antiviral, and anticancer drugs.

The Uses of PHORBOL

Phorbol is a plant-derived diterpene that exhibits various biological activities such as its role as tumor promoters through the activation of protein kinase C.

What are the applications of Application

Phorbol is a plant-derived diterpene that is a tumor promoter

Definition

ChEBI: A diterpenoid with the structure of tigliane hydroxylated at C-4, -9, -12(beta), -13 and -20, with an oxo group at C-3 and unsaturation at the 1- and 6-positions.

Preparation

Phorbol can be extracted from croton oil by two-phase alcoholysis and purified by high-speed counter-current chromatography^[1]. The specific method is as follows:
The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.

General Description

White solid.

Air & Water Reactions

Water soluble.

Reactivity Profile

PHORBOL is unstable to prolonged exposure to air, light and ambient temperatures. PHORBOL is also sensitive to acid and alkalis and is subject to autooxidation. PHORBOL dissolves slowly, therefore solution in a desired solvent is best accomplished by prolonged shaking under an inert atmosphere. .

Fire Hazard

PHORBOL is probably combustible.

Toxicology

Toxicity of Phorbol: Dermal (mouse) LD50: 36 mg - mild, Unlike its diesters, phorbol does not appear to be a co-carcinogen or to enhance chemical mutagenesis. Evidence of carcinogenicity is limited. Highly toxic by inhalation, in contact with skin and if swallowed. Irritating to eyes, respiratory system and skin.

References

[1] JIE-PING FAN. Biphasic alcoholysis coupled with high-speed countercurrent chromatography for high performance on separating phorbol from Croton tiglium Linn extracts[J]. Journal of separation science, 2023. DOI:10.1002/jssc.202200984.