 | |
| Names | |
|---|---|
| IUPAC name (13R)-1α,6β,9α-Trihydroxy-11-oxo-8α,13-epoxylabd-14-en-7β-yl acetate | |
| Systematic IUPAC name (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-Ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxododecahydro-1H-naphtho[2,1-b]pyran-5-yl acetate | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| DrugBank |
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| ECHA InfoCard | 100.060.354 |
| UNII | |
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| Properties | |
| C22H34O7 | |
| Molar mass | 410.507 g·mol−1 |
| Solubility | Soluble in organic solvents such as ethanol, chloroform and DMSO[1] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Forskolin (coleonol) is alabdanediterpene produced by the plantColeus barbatus (blue spur flower). Other names include pashanabhedi, Indian coleus, makandi, HL-362, mao hou qiao rui hua.[2] As with other members of the largediterpene class of plant metabolites, forskolin is derived fromgeranylgeranyl pyrophosphate (GGPP). Forskolin contains some unique functional elements, including the presence of atetrahydropyran-derivedheterocyclic ring.
Forskolin is commonly used in laboratory research to increase levels ofcyclic AMP by stimulation ofadenylate cyclase.[2]
The name comes from an obsolete name for the plant,Plectranthus forskolaei (seeColeus barbatus).
Forskolin is used inbiochemistry experiments to raise levels ofcyclic AMP (cAMP) in studies ofcell physiology.[2][3] Forskolin activates the enzymeadenylyl cyclase and increases intracellular levels of cAMP. cAMP is an importantsecond messenger necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in thehypothalamus-pituitary gland axis, and for the feedback control of hormones via induction ofcorticotropin-releasing factor gene transcription.[4] Cyclic AMP acts by activating cAMP-sensitive pathways such asprotein kinase A andEPAC1.
It is defined as a category 4 chemical with acute dermal toxicity based on 2012 OSHA Hazard Communication Standard (29 CFR 1910.1200).[5]
Its derivatives includecolforsin daropate,NKH477,[6] andFSK88,[7] which may be more potent than forskolin at raising cAMP. These derivatives may have pharmaceutical utility againstbronchoconstriction andheart failure.[8][9]
A total chemical synthesis has been reported. The key step of this chemical synthesis is photocyclization of a synthetic intermediate in presence of oxygen and methylene blue, followed by a singlet oxygen Diels-Alder reaction.[10]
The heterocyclic ring is synthesized after the formation of the trans-fused carbon ring systems formed by acarbocation mediatedcyclization. The remaining tertiarycarbocation is quenched by a molecule of water. Afterdeprotonation, the remaininghydroxy group is free to form the heterocyclic ring. This cyclization can occur either by attack of the alcohol oxygen onto theallylic carbocation formed by loss ofdiphosphate, or by an analogousSN2'-like displacement of the diphosphate.[11] This forms the core ring system A of forskolin.
The remaining modifications of the core ring system A can putatively be understood as a series of oxidation reactions to form a poly-ol B which is then further oxidized andesterified to form theketone andacetate ester moieties seen in forskolin. However, because the biosynthetic gene cluster has not been described, this putative synthesis could be incorrect in the sequence of oxidation/esterification events, which could occur in almost any order.
Although forskolin has been used in preliminary weight loss research, the low quality of the studies and inconclusive results prevented any determination of effects.[12]
