15291-77-7

Basic information

• Product Name: Ginkgolide B
• Synonyms: BN 52021;GINKGOLIDE B;ginkgolide B from ginkgo leaves;(1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11R,11aR)-3-(1,1-Dimethylethyl)hexahydro-4,7b,11-trihydroxy-8-methyl-9H-1,7a-(epoxymethano)-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione;ginkgolide b from ginkgo biloba leaves;GinkgolideA,1-hydroxy-, (1β)-;GINKGOLIDE B(SH);Ginkgolide B, froM Ginkgo biloba
• CAS NO: 15291-77-7
• Molecular Formula: C₂₀H₂₄O₁₀
• Molecular Weight: 424.4
• EINECS: 604-876-0
• Product Categories: Saponins;Intermediates & Fine Chemicals;Pharmaceuticals;PAF receptor;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 15291-77-7.mol

Chemical Properties

• Melting Point: 280°C (dec.)
• Boiling Point: 762.416 °C at 760 mmHg
• Flash Point: 274.337 °C
• Appearance: white crystal powder
• Density: 1.645 g/cm³
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 40 mg/ml) or in Ethanol (up to 10 mg/ml).
• PKA: pKa1 7.14; pKa2 8.60; pKa3 11.89(at 25℃)
• Water Solubility: Soluble in DMSO. Slightly soluble in water and ethanol
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months
• BRN: 4727611
• CAS DataBase Reference: Ginkgolide B(CAS DataBase Reference)
• NIST Chemistry Reference: Ginkgolide B(15291-77-7)
• EPA Substance Registry System: Ginkgolide B(15291-77-7)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• F: 10-21
• Hazardous Substances Data: 15291-77-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
Ginkgolide B is used as a potent PAF-R antagonist for its various therapeutic effects. It speeds up PAF hydrolysis by promoting PAF-AH I α2 homodimer activity, inhibits neutrophil degranulation in vitro, and superoxide production. Additionally, it demonstrates neuroprotective properties following oral administration in vivo.
Used in Cerebral Ischemic Disease Treatment:
Ginkgolide B is employed in the treatment of cerebral ischemic diseases due to its ability to promote blood circulation and remove blood stasis. Its use in this application has been supported by traditional Chinese medicine practices and further research into its effectiveness as a small molecule drug.
Used in Neuroprotection:
Ginkgolide B is used as a neuroprotective agent following oral administration in vivo. Its neuroprotective properties make it a valuable compound in the development of treatments for various neurological conditions.
Used in Inflammation and Immune Response Modulation:
Ginkgolide B is used to inhibit bronchoconstriction and modulate the immune response by inhibiting neutrophil degranulation and superoxide production. This application makes it a potential candidate for the treatment of inflammatory and immune-related disorders.

History

The leaf of Ginkgo biloba is sweet, bitter, astringent, and mild. With activating blood circulation to remove blood stasis, dredging collaterals, relieving pain, and asthma, it is applied for treating blood stasis, chest pain, stroke, lung deficiency cough, and hyperlipidemia.As early as in the 1930s, scientists began to study ginkgo and harvest a variety of ginkgolide . Ginkgolide B was isolated and its structure illustrated by Wan Shan et?al. in 1967. Subsequently, it was synthesized by Corey et?al. in 1988. The preparation of effective components of Ginkgo biloba has been listed at home and abroad with development.The Ginkgo biloba extract consisting of ticlopidine is widely used in overseas market for the treatment of cerebral infarction. Intravenous injection of ginkgolide B is applied for the treatment of inflammation, but the project has been in the state, and there is no progress in it for many years. In addition, whether other extract of Ginkgo biloba can be used for the treatment of stable angina, cognitive impairment is still in preclinical research status.

Indications

The injection consists of multiple components, and there are three kinds of substance mainly in diterpene ginkgolides meglumine injection. It promotes blood circulation by removing blood stasis and activates the channels and collaterals for cerebral ischemia treatment.

Biological Activity

Platelet-activating factor (PAF) receptor antagonist (K i = 1.3 μ M). Inhibits neutrophil degranulation and superoxide production in vitro and inhibits bronchoconstriction and is neuroprotective following oral administration in vivo .

Pharmacology

Ginkgolide B has a variety of pharmacological effects, mainly in cardiovascular and cerebrovascular protection and neuroprotection. On the one hand, with the strongest activity in nature, the platelet-activating factor (PAF) receptor antagonist is recognized by the public . PAF can inhibit the downstream inflammatory cascade for anti-inflammatory. It also can alleviate cerebral infraction volume and cerebral edema induced by cerebral ischemia among the animal model of cerebral ischemia reperfusion through unknown mechanism. By inhibiting NF-κB and TNF-α, the apoptosis of nerve cell can be alleviated. The compound protects the abdominal cavity and intestinal tract by inhibiting release of neutrophil chemotactic protein by macrophage.

Clinical Use

Oral and injection preparations are applied widely in clinical therapy. Made in oral preparation, flavonoids are the main component of raw material. There are little chemical compounds in injection, and ginkgolides are the main component whose content is different from each other. Listed ginkgolide injection is applied for ischemia stroke formed by blood stasis with promoting blood circulation by removing blood stasis and clearing and activating the channels and collaterals. Compared with Shuxuening injection in clinical trials, ginkgolides injection is consistent in improving indicators effect, such as protection in nerve injury and others.

References

1) Foldes-Filep et al. (1987), Inhibition by BN 52021 (ginkgolide B) of the binding of [3H]-platelet-activating factor to human neutrophil granulocytes; Biochem. Biophys. Res. Commun., 148 1412 2) Desquand et al. (1986), Interference of BN 52021 (ginkgolide B) with the bronchopulmonary effects of PAF-acether in the guinea-pig; Eur. J. Pharmacol., 127 83 3) Maclennan et al. (2002), The CNS effects of Ginko biloba extracts and ginkgolide B; Prog. Neurobiol., 67 235 4) Li et al. (2013), Neuroprotective effect of ginkogolide B on bupivacaine-induced apoptosis in SH-SY5Y cells; Oxid. Med. Cell. Longev., 2013 159864 5) Wang et al. (2014), Neuroprotection against permanent focal cerebral ischemia by ginkgolides A and B is associated with obstruction of the mitochondrial apoptotic pathway via inhibition of c-Jun N-terminal kinase in rats; J. Neurosci. Res., 92 232

Synthetic route

α-benzylginkgolide B (170288-58-1) → ginkgolide B (15291-77-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol under 2888 Torr; for 24h;	97%

1-O-(tert-Butyldiphenylsilyl)ginkgolid B (130523-06-7) → ginkgolide B (15291-77-7)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 2h;	73%

C28H32O11 (145473-36-5) → ginkgolide B (15291-77-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol at 23℃; under 760 Torr; for 5h; Yield given;

7-trifluoromethanesulfonyloxy ginkgolide B (173102-79-9) → ginkgolide B (15291-77-7)

Conditions	Yield
With tetrabutylammonium borohydride

1,3,7,10-Tetrahydroxyginkgolid (15291-76-6) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: nBu4NBH4 View Scheme

gingkolide C (15291-76-6, 119322-55-3) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: diisopropylethylamine / acetonitrile / 5 h / 0 °C 2: 63 percent / 4-N,N-dimethylaminopyridine / acetonitrile / 12 h / 5 °C 3: tri-n-butyltin hydride, bisazoisobutyronitrile / benzene / 12 h / Heating 4: H2 / Pd-C / methanol / 5 h / 23 °C / 760 Torr View Scheme

C28H32O12 (145497-37-6) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 63 percent / 4-N,N-dimethylaminopyridine / acetonitrile / 12 h / 5 °C 2: tri-n-butyltin hydride, bisazoisobutyronitrile / benzene / 12 h / Heating 3: H2 / Pd-C / methanol / 5 h / 23 °C / 760 Torr View Scheme

C35H31F5O13S (145497-38-7) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: tri-n-butyltin hydride, bisazoisobutyronitrile / benzene / 12 h / Heating 2: H2 / Pd-C / methanol / 5 h / 23 °C / 760 Torr View Scheme

Ginkgolide C (15291-76-6) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 95 percent / imidazole / dimethylformamide / 48 h 2: 66 percent / DMAP / acetonitrile / 24 h 3: 93 percent / tributyltin hydride, AIBN / toluene / 3 h / Heating 4: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme

1-O-(tert-Butyldiphenylsilyl)ginkgolid C (130523-04-5) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 66 percent / DMAP / acetonitrile / 24 h 2: 93 percent / tributyltin hydride, AIBN / toluene / 3 h / Heating 3: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme

1-O-(tert-Butyldiphenylsilyl)-7-O-(phenyloxythiocarbonyl)ginkgolid C (130523-05-6) → ginkgolide B (15291-77-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / tributyltin hydride, AIBN / toluene / 3 h / Heating 2: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme

1-Chloro-4-(chloromethyl)benzene (104-83-6) + ginkgolide B (15291-77-7) → 10-O-p-chlorobenzylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	98.3%

ginkgolide B (15291-77-7) + tert-butylchlorodiphenylsilane (58479-61-1) → 1-(tert-butyldiphenylsilyloxy)-3,10-dihydroxyginkgolid (130523-06-7)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide for 48h; Ambient temperature;	98%

ginkgolide B (15291-77-7) + 1-chloromethyl-4-fluorobenzene (352-11-4) → 10-O-p-fluorobenzylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	96.7%

(2-chloroethyl)dimethylamine hydrochloride (4584-46-7) + ginkgolide B (15291-77-7) → 10-O-(2-dimethylaminoethyl)ginkgolide B (914251-20-0)

Conditions	Yield
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; Reagent/catalyst; Temperature; Flow reactor;	94.1%
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; for 0.05h; Reagent/catalyst; Temperature; Concentration; Flow reactor;	94.1%

4-nitrobenzyl chloride (100-14-1) + ginkgolide B (15291-77-7) → 10-O-p-nitrobenzylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	92.3%

ginkgolide B (15291-77-7) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 10-O-p-methoxyphenacylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	90.1%

chloroformic acid ethyl ester (541-41-3) + ginkgolide B (15291-77-7) → 10-O-ethoxycarbonylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Acylation; Heating;	89.4%

ginkgolide B (15291-77-7) + 1-chloroacetophenone (532-27-4) → 10-O-phenacylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	89.2%

1-hydroxybenzotriazolyl acetate (18355-05-0) + ginkgolide B (15291-77-7) → C20H24O10(CH2CO) + C20H24O10(CH2CO)

Conditions	Yield
With pyridine; dmap In N,N-dimethyl-formamide	A 88% B 9%

ginkgolide B (15291-77-7) + allyl bromide (106-95-6) → 10-O-allylginkgolide B (289490-32-0)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	87.8%

N-methyl-2-chloroethylamine hydrochloride (4535-90-4) + ginkgolide B (15291-77-7) → 10-O-methylaminoethyl ginkgolide B (914251-23-3)

Conditions	Yield
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; Flow reactor;	83.5%

2-chloroethanamine hydrochloride (870-24-6) + ginkgolide B (15291-77-7) → 10-O-aminoethyl ginkgolide B

Conditions	Yield
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; Flow reactor;	79.4%

ginkgolide B (15291-77-7) + ethyl bromoacetate (105-36-2) → 10-O-ethyloxycarbonylmethylginkgolide B + 1-O-ethyloxycarbonylmethylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	A 78.3% B 12.1%

ginkgolide B (15291-77-7) + 2-chloro-ethanol (107-07-3) → 10-O-hydroxyethyl ginkgolide B

Conditions	Yield
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; Flow reactor;	76.3%
With calcium carbonate; potassium iodide In water; acetonitrile at 85℃; for 0.05h; Flow reactor;	76.3%

4-bromobut-2-enenitrile (42879-03-8) + ginkgolide B (15291-77-7) → 10-O-(3-cyanoallyl)ginkgolide B

Conditions	Yield
With triethylamine; potassium iodide In chloroform Reflux;	75%

ginkgolide B (15291-77-7) + 4-Methylbenzyl bromide (104-81-4) → 10-O-p-methylbenzylginkgolide B (170288-73-0)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 75℃; for 0.75h;	72.9%

1-bromomethyl-4-iodobenzene (16004-15-2) + ginkgolide B (15291-77-7) → 10-O-p-iodobenzylginkgolide B (170289-24-4)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 70℃; for 0.666667h;	72.4%

ginkgolide B (15291-77-7) + 2-bromopropionitrile (19481-82-4) → 10-O-(1-cyanoethyl)ginkgolide B

Conditions	Yield
With triethylamine; potassium iodide In chloroform Reflux;	71%

benzyl chloride (100-44-7) + ginkgolide B (15291-77-7) → α-benzylginkgolide B (170288-58-1)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	65.3%

ginkgolide B (15291-77-7) + propargyl bromide (106-96-7) → 10-O-propargylated ginkgolide B

Conditions	Yield
With potassium carbonate In acetonitrile for 24h; Reflux; Inert atmosphere;	65%
With potassium carbonate; potassium iodide In acetonitrile at 100℃; for 2.5h;

ginkgolide B (15291-77-7) + 1-bromomethyl-4-bromobenzene (589-15-1) → 10-O-p-bromobenzylginkgolide B (170289-51-7)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 70℃; for 0.833333h;	64.5%

formaldehyd (50-00-0) + ginkgolide B (15291-77-7) → 1,10-O,O-methyleneginkgolide B

Conditions	Yield
With sulfuric acid; acetic acid In tetrahydrofuran for 8h; Condensation; Heating;	61.8%

3,5-dinitrobenzoic acid (99-34-3) + ginkgolide B (15291-77-7) → C27H26N2O15

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 6h;	61.25%

ginkgolide B (15291-77-7) + methyl iodide (74-88-4) → 1-O-methylginkgolide B + 10-O-methylginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile for 0.5h; Alkylation; Heating;	A 26.7% B 60.1%

bromoacetic acid tert-butyl ester (5292-43-3) + ginkgolide B (15291-77-7) → 10-O-(tert-butoxyformylmethyl)ginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In tetrahydrofuran for 2h; Reflux;	58%

ginkgolide B (15291-77-7) + methyl 2-(2-iodoethoxy)acetate (84424-42-0) → 10-O-(methoxyformylmethoxyethyl)ginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In tetrahydrofuran for 2h; Reflux;	58%

methyl bromoethoxyethoxyacetate + ginkgolide B (15291-77-7) → 10-O-(methoxyformylmethoxyethoxyethyl)ginkgolide B

Conditions	Yield
With potassium carbonate; potassium iodide In tetrahydrofuran for 2h; Reflux;	56%

ginkgolide B (15291-77-7) + 4-methoxybenzoic acid (100-09-4) → C28H30O12 + C28H30O12

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 6h;	A 8.4% B 55.57%

Upstream product

• 130523-06-7 1-O-(tert-Butyldiphenylsilyl)ginkgolid B 
• 145473-36-5 C₂₈H₃₂O₁₁ 
• 173102-79-9 7-trifluoromethanesulfonyloxy-ginkgolide C 
• 170288-58-1 α-benzylginkgolide B 
• 15291-76-6 1,3,7,10-Tetrahydroxyginkgolid 
• 15291-76-6 ginkgolide C 
• 15291-76-6 Ginkgolide C 
• 130523-05-6 1-O-(tert-Butyldiphenylsilyl)-7-O-(phenyloxythiocarbonyl)ginkgolid C 
• 112574-09-1 C₂₆H₃₈O₁₀Si 
• 112532-64-6 2-(2,2-dimethoxyethyl)-2-cyclopenten-1-one 
• 112574-07-9 C₂₀H₂₄O₈ 
• 112532-66-8 (5S,9R)-9-tert-Butyl-3-methoxy-2-oxa-spiro[4.4]nonan-6-one 
• 112532-65-7 [3-tert-Butyl-2-(2,2-dimethoxy-ethyl)-cyclopent-1-enyloxy]-trimethyl-silane 
• 112532-77-1 C₁₉H₂₈O₅ 

Downstream Products

• 130523-06-7 1-(tert-butyldiphenylsilyloxy)-3,10-dihydroxyginkgolid 
• 201736-27-8 1-O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)ginkgolide B 
• 201736-29-0 10-O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)ginkgolide B 
• 201736-30-3 10-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)ginkgolide B 
• 170288-58-1 α-benzylginkgolide B 
• 153355-70-5 ginkgolide K 
• 153355-69-2 1-(tert-butyldiphenylsilyloxy)-10-hydroxy-3,14-didehydroginkgolid 

Related news

Ginkgolide B (cas 15291-77-7) and bilobalide ameliorate neural cell apoptosis in α-synuclein aggregates08/04/2019

The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), a chronic progressive neurodegenerative disorder. Extensive evidences have shown the promising effects of Ginkgo biloba consumption on motor activity after PD. ...detailed

Ginkgolide B (cas 15291-77-7) enhances gemcitabine sensitivity in pancreatic cancer cell lines via inhibiting PAFR/NF-кB pathway08/03/2019

Gemcitabine resistance will occur by time after the initial response in pancreatic cancer. Ginkgolide B (GB), a major terpene lactone component of Ginkgo biloba leaves, is a highly selective and competitive inhibitor for platelet-activating factor (PAF) receptor. In the present study, we evaluat...detailed

Relevant articles and documents

Preparation of a tritiated ginkgolide

A radiolabeled constituent of Ginkgo biloba, [3H]-ginkgolide B, was prepared in high specific radioactivity, providing a tool for studying neuromodulatory properties of ginkgolides. Ginkgolide B, a constituent of the tree Ginkgo biloba, was radiolabeled with the β-emitter tritium ([ 3H]) in two steps from ginkgolide C. First, a triflate precursor was prepared utilizing the selective reactivity of 7-OH in ginkgolide C; the triflate was then reduced with sodium borotritide to yield tritiated ginkgolide B ([3H]GB) in good yield and high specific activity. The tritiated ginkgolide will be an important tool for studying neuromodulatory properties of ginkgolides.

Isolation of ginkgolides A, B, C, J and bilobalide from G. biloba extracts

Ginkgolides A, B, C and J, together with bilobalide, are unique terpenoid components of the Ginkgo biloba tree. Due to similar chemical properties, their separation is quite tedious. We have developed an efficient and rapid protocol for separation of individual ginkgolides and bilobalide from G. biloba extracts. The procedure takes advantage of enhanced susceptibility of ginkgolides B and C to benzylation and the ease of separation of these products from ginkgolides A and J which do not react. The protocol is applicable to the previously reported enriched extracts prepared from G. biloba leaves. A single chromatographic step prior to benzylation provides bilobalide and mixture of ginkgolides A, B, C, and J. After benzylation, the individual ginkgolides are separated by chromatography.

INTRAMOLECULAR AND INTERMOLECULAR HYDROXYL REACTIVITY DIFFERENCES IN GINKGOLIDES A, B AND C AND THEIR CHEMICAL APPLICATIONS

An investigation of the chemistry of ginkgolides A, B and C (1) has revealed an unusual interaction between the hydroxyl groups at C(1) and C(10) which activates their deprotonation to give 2 and provides a method for the interconversion of 1C and 1B.The ginkgolide 7-enol system 7 is more stable than the corresponding 7-keto form 6, which is easily made by selective Jones oxydation of ginkgolide C.

Chemistry of Ginkgolides, IV. Synthesis of Ginkgolide B from Ginkgolide C

The reaction of ginkgolide C (3) with tert-butylchlorodiphenylsilane results exclusively in the formation of the 1-O-tert-butyldiphenylsilyl ether 5, which when treated with O-phenylchlorothioformate leads to the 7-phenyloxythiocarbonyl derivative 6.The reduction of 6 with tributyltin hydride/AIBN yields the 1-O-tert-butyldiphenylsilyl ether 7 of ginkgolide B (2).Removal of the silyl protective group with tetrabutylammonium fluoride gives pure ginkgolide B (2).The structures of the reaction products were confirmed by analytical and spectroscopic methods.