Ginkgolides

Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba. They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate. Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba. They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate. Ginkgolide B, specifically, is a diterpenoid trilactone with six five-membered rings. It contains a spiro-nonane carbocyclic ring, a tetrahydrofuran ring, and a very specific tert-butyl group at one of the rings (Figure 1).The class of ginkgolides was first isolated from the tree Ginkgo biloba in 1932. Structural elucidation was accomplished in 1967 by Maruyama et al. It is extracted from the root bark and leaves of the Ginkgo 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. This class of molecules has been studied for its potential to act as a platelet-activating factor receptor antagonist. 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. Ginkolides A - C were isolated from a large scale methanolic 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. Therefore, studying the biosynthesis of the molecule is preferable. 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.