Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba . They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate. [1]
Ginkgolides are biologically active terpenic lactones present in Ginkgo biloba . They are diterpenoids with 20-carbon skeletons, which are biosynthesized from geranylgeranyl pyrophosphate. [1]
| Name | R1 | R2 | R3 |
| Ginkgolide A | OH | H | H |
| Ginkgolide B | OH | OH | H |
| Ginkgolide C | OH | OH | OH |
| Ginkgolide J | OH | H | OH |
| Ginkgolide M | H | OH | OH |
Ginkgolide B, specifically, is a diterpenoid trilactone with six five-membered rings. It contains a spiro[4,4]-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. [2] Structural elucidation was accomplished in 1967 by Maruyama et al. [3]
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. [4]
This class of molecules has been studied for its potential to act as a platelet-activating factor receptor antagonist. [2] [5]
Ginkgolide B has been investigated for its potential to reducing migraine frequency. [6]
Ginkgolide B is also used in treatment for cerebrovascular disease. Research has also proven that ginkgolide B can also treat migraines in young ages. [2] [4] [6] 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. [5]
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. [2] 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.
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 alkenes, 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 alkenes generates (9) intermediate which then undergoes ring closures featuring one hemiacetal and all three lactones to get ginkgolide B at (10). [4]
Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.
A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium CH+
3, methanium CH+
5 and vinyl C
2H+
3 cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountered.
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries a partial positive charge, or have an atom that does not have an octet of electrons.
Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba.
Diterpenes are a class of terpenes composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being a primary intermediate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and anti-inflammatory.
Geranylgeranyl pyrophosphate is an intermediate in the biosynthesis of diterpenes and diterpenoids. It is also the precursor to carotenoids, gibberellins, tocopherols, and chlorophylls.
Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins.
In enzymology, bornyl diphosphate synthase (BPPS) (EC 5.5.1.8) is an enzyme that catalyzes the chemical reaction
In enzymology, a copalyl diphosphate synthase is an enzyme that catalyzes the chemical reaction
In enzymology, an ent-copalyl diphosphate synthase is an enzyme that catalyzes the chemical reaction:
The enzyme abieta-7,13-diene synthase catalyzes the chemical reaction
The enzyme taxadiene synthase catalyzes the chemical reaction
Phytoene is a 40-carbon intermediate in the biosynthesis of carotenoids. The synthesis of phytoene is the first committed step in the synthesis of carotenoids in plants. Phytoene is produced from two molecules of geranylgeranyl pyrophosphate (GGPP) by the action of the enzyme phytoene synthase. The two GGPP molecules are condensed together followed by removal of diphosphate and proton shift leading to the formation of phytoene.
The vinyl cation is a carbocation with the positive charge on an alkene carbon. Its empirical formula is C
2H+
3. More generally, a vinylic cation is any disubstituted carbon, where the carbon bearing the positive charge is part of a double bond and is sp hybridized. In the chemical literature, substituted vinylic cations are often referred to as vinyl cations, and understood to refer to the broad class rather than the C
2H+
3 variant alone. The vinyl cation is one of the main types of reactive intermediates involving a non-tetrahedrally coordinated carbon atom, and is necessary to explain a wide variety of observed reactivity trends. Vinyl cations are observed as reactive intermediates in solvolysis reactions, as well during electrophilic addition to alkynes, for example, through protonation of an alkyne by a strong acid. As expected from its sp hybridization, the vinyl cation prefers a linear geometry. Compounds related to the vinyl cation include allylic carbocations and benzylic carbocations, as well as aryl carbocations.
Momilactone B is an allelopathic agent produced from the roots of rice. It has been shown to be produced in high concentrations by the roots of rice seedlings. The production of momilactone B has also been induced in response to infection by blast fungus or irradiated with UV light. More recently it has been shown to be a potential chemotherapeutic agent against human colon cancer.
Absinthin is a naturally produced triterpene lactone from the plant Artemisia absinthium (Wormwood). It constitutes one of the most bitter chemical agents responsible for absinthe's distinct taste. The compound shows biological activity and has shown promise as an anti-inflammatory agent, and should not be confused with thujone, a neurotoxin also found in Artemisia absinthium.
Juvabione, historically known as the paper factor, is the methyl ester of todomatuic acid. Both are sesquiterpenes (C15) found in the wood of true firs of the genus Abies. They occur naturally as part of a mixture of sesquiterpenes based upon the bisabolane scaffold. Sesquiterpenes of this family are known as insect juvenile hormone analogues (IJHA) because of their ability to mimic juvenile activity in order to stifle insect reproduction and growth. These compounds play important roles in conifers as the second line of defense against insect induced trauma and fungal pathogens.
In molecular biology, this protein domain belongs to the terpene synthase family (TPS). Its role is to synthesize terpenes, which are part of primary metabolism, such as sterols and carotene, and also part of the secondary metabolism. This entry will focus on the C terminal domain of the TPS protein.
Geosmin synthase or germacradienol-geosmin synthase designates a class of bifunctional enzymes that catalyze the conversion of farnesyl diphosphate (FPP) to geosmin, a volatile organic compound known for its earthy smell. The N-terminal half of the protein catalyzes the conversion of farnesyl diphosphate to germacradienol and germacrene D, followed by the C-terminal-mediated conversion of germacradienol to geosmin. The conversion of FPP to geosmin was previously thought to involve multiple enzymes in a biosynthetic pathway.
Levopimaradiene synthase is an enzyme with systematic name (+)-copalyl-diphosphate diphosphate-lyase . This enzyme catalyses the following chemical reaction