Product Code Database
Ginkgolides are biologically active terpenoid present in Ginkgo biloba. They are with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate.
| +Ginkgolides |
| R3 |
| H |
| H |
| OH |
| OH |
| OH |
Ginkgolide B has been investigated for its potential to reducing migraine frequency.
Ginkgolide B is also used in treatment for cerebrovascular disease. Research has also proven that ginkgolide B can also treat migraines in young ages. The literature indicates that ginkgolide B functions as a selective antagonist of glycine receptors based on noncompetitive inhibition for the neurological system that this compound performs.
Most of the natural product terpenoids start with isopentenyl diphosphate synthesized by the MEP pathway. This pathway also generates dimethylallyl diphosphate, from pyruvate and D-glyercaldehyde 3-phosphate (GAP). When coupled together, they form one molecule of geranylgeranyl diphosphate with geranylgeranyl diphosphate synthase.
A molecule of GGPP generates ( 1) (+)-copalyl in the presence of levopimaradiene synthase. ( a) Then ( 1) loses its OPP group catalyzed by this same synthase, performing an intramolecular allylic cyclization with the two Alkene, to form ( 2) the sandaracopimarenyl cation. ( b) This cation then undergoes an internal cyclization to stabilize the carbocation 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 tertiary carbocation 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 formed abietatriene 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 with Alkene generates ( 9) intermediate which then undergoes Cyclic compound featuring one hemiacetal and all three lactones to get ginkgolide B at ( 10).
Spectroscopic studies for the elucidation of the individual structures for the ginkgolides
Ginkolides A - C were isolated from a large scale 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.
Biosynthesis of ginkgolide B
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. Therefore, studying the biosynthesis of the molecule is preferable.
See also
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