Ginkgolide A has a chemical formula of C20H24O9, itsCAS No. is 15291-75-5.[2]
Aside from the G. Biloba tree, this ginkgolide has also been reported to be present inMachilus wangchiana.[3] It is also biologically active.
A study has concluded that Ginkgolide A can induce theCYP1A2 enzyme, but not as much as other chemicals present in Ginkgo.[4] This means that Ginkgolide A can increase the action of CYP1A2. Ginkgolide A also acts as an antagonist of glycine receptors[5][6] and α1β2γ2L GABAA receptors.[7] Additionally, it acts as a powerfulPAF antagonist.[8]
Ginkgolide B, specifically, is a diterpenoid trilactone with six five-membered rings. It contains a spiro[4,4]-nonane carbocyclic ring, atetrahydrofuran ring, and a very specifictert-butyl group at one of the rings (Figure 1).The class of ginkgolides was first isolated from the treeGinkgo biloba in 1932.[9] Structural elucidation was accomplished in 1967 by Maruyamaet al.[10]
It is extracted from the root bark and leaves of theGinkgo biloba (ginkyo meaning "silver apricot") tree found native in China. It is marketed to other countries that include Korea, France, the United States, etc. for the drug and clinical properties of the extracts. Present in the tree is less than 0.1 to 0.25% of ginkgolide B, the most abundant being ginkgolide A.[11]
Ginkgolide B has been investigated for its potential to reducing migraine frequency.[13]
Ginkgolide B is also used in treatment forcerebrovascular disease. Research has also proven that ginkgolide B can also treat migraines in young ages.[9][11][13] The literature indicates that ginkgolide B functions as a selective antagonist ofglycine receptors based on noncompetitive inhibition for the neurological system that this compound performs.[12]
Spectroscopic studies for the elucidation of the individual structures for the ginkgolides
Ginkolides A - C were isolated from a large scalemethanolic extraction followed by liquid-liquid partitions, column chromatography and repeated crystallizations. The molecular formulas were determined by high resolution mass spectrometry, and the overall structures by IR and NMR spectroscopic analysis and extensive derivitization techniques.
While researchers have published chemical pathways to make this molecule, most of the designed syntheses were too complex and produced little of the actual material to run full analyses.[9] Therefore, studying the biosynthesis of the molecule is preferable.
A molecule ofGGPP generates (1) (+)-copalyl in the presence oflevopimaradiene synthase. (a) Then (1) loses its OPP group catalyzed by this same synthase, performing an intramolecular allylic cyclization with the twoalkenes, to form (2) the sandaracopimarenyl cation. (b) This cation then undergoes an internal cyclization to stabilize thecarbocation in the ring by proton transfer to form (3) intermediate.(c) By doing this, the molecule sets itself up for a methyl migration to stabilize that secondary cation and generate that tertiarycarbocation at (4). (d) This induces a loss of proton to get (5) levopimaradiene. (e) With oxidation, a loss of a proton to form an aromatic ring generates (6)abietatriene. (g) This newly formedabietatriene undergoes a 1,2-alkyl shift to break the 6-membered ring into (7) with a five-membered ring (more favorable). (h) Another 1,2-alkyl shift takes place at the same time a ring cleavage takes place to generate (8). (i) Oxidation at all the positions withalkenes generates (9) intermediate which then undergoesring closures featuring onehemiacetal and all threelactones to get ginkgolide B at (10).[11]
^Maruyama, M.; Terahara, A.; Itagaki, Y.; Nakanishi, K. (1967). "The ginkgolides. I. Isolation and characterization of the various groups".Tetrahedron Letters.8 (4):299–302.doi:10.1016/S0040-4039(00)71538-3.
^abcDewick, P.M. (2012).Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). United Kingdom: John Wiley and Sons, Ltd. pp. 230–232.ISBN978-0470741672.
