Chemie der Ginkgolide, I. 10‐Acetyl‐1‐methoxycarbonyl‐2,3,14,15,16‐pentanorginkgolid A, ein Zwischenprodukt zur Herstellung von Bilobalid

Weinges, Klaus; Hepp, M.; Huber‐Patz, U.; Rodewald, H.; Irngartinger, Hermann

doi:10.1002/jlac.198619860610

Cited by 17 publications

(5 citation statements)

References 5 publications

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“…The base instability of bilobalide might derive from its rapid rearrangement to iso -bilobalide. A similar rearrangement had been observed by Weinges and co-workers upon treatment of bilobalide with acetic anhydride and pyridine, which delivered diacetoxy- iso -bilobalide . However, we found rearrangement occurred simply upon treatment with base (Figure a).…”

Section: Results and Discussionmentioning

confidence: 99%

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

et al. 2020

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Here we interrogate the structurally dense (1.63 mcbits/Å 3 ) GABA A receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. 13 C isotope labeling identifies an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal persists in concentrated mineral acid (1.5 M DCl in THF-d 8 /D 2 O); its longevity is correlated to destabilizing steric clash between substituents upon ring-opening. Second, a regioselective oxidation of des-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. We also establish equivalent effects of (−)-bilobalide and the nonconvulsive sesquiterpene (−)-jiadifenolide on action potential-independent inhibitory currents at GABAergic synapses, using (+)-bilobalide as a negative control. The high information density of bilobalide distinguishes it from other scaffolds, and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (ca. 132,000 molecules/minute) calculate information content (Böttcher scores), which may prove helpful to identify important features of NP space.

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Section: Results and Discussionmentioning

confidence: 99%

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

et al. 2020

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“…While Ginkgo biloba achieves total biosynthesis of ginkgolides with great ease, it is only recently that chemical synthesis of these compounds has been accomplished. Weinges and colleagues reported the synthesis of hexahydro-5H-dicyclopenta[b, clfuran-5a(6H)-ol, which represents the main framework of ginkgolides (rings A, B, D) ) and partial synthesis of bilobalide from ginkgolide A and B (Weinges et al, 1986). The synthesis of the bicyclic keto ester, a potential intermediate for the synthesis of Ginkgo biloba terpenoids, has also been described by Corey et af.…”

Section: Ginkgolidesmentioning

confidence: 94%

Natural antagonists of platelet‐activating factor

Hosford

Mencia‐Huerta

Page

et al. 1988

Phytotherapy Research

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Several groups of antagonists of platelet-activating factor (PAF) are reviewed. The characteristics of PAF binding sites on mammalian cell membranes are described together with the activities of non-specific and synthetic PAF-antagonists. The specificity of the ginkgolides to bind to PAF-receptors is discussed and the effects of these natural products in a range of biological systems is emphasized. Other groups of natural PAF-antagonists described are the lignans and gliotoxin related compounds. The structural chemistry, structure-activity relationships and pharmacological properties of these drugs are compared to the ginkgolides.

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“…[78] Weinges et al carried out numerous synthetic studies of ginkgolides and bilobalide. [133][134][135][136][137][138] A recent study described an Scheme 9. Total synthesis of GB (2) by Crimmins and co-workers.…”

Section: Synthetic Modification Of Parent Compoundsmentioning

confidence: 98%

“…[78] Weinges et al carried out numerous synthetic studies of ginkgolides and bilobalide. [133][134][135][136][137][138] A recent study described an approach to the preparation of radiolabeled analogues of ginkgolides, in this case [ 14 C]GA, although the actual radioligand was not synthesized. [139] GA (1) was partially degraded as previously described, [135,136,138] and this was followed by incorporation of the lithium enolate of methyl propionate, which could be [ 14 C]-labeled, and subsequent ring closure to give GA (1).…”

Section: Synthetic Modification Of Parent Compoundsmentioning

confidence: 99%

Chemistry and Biology of Terpene Trilactones fromGinkgo Biloba

2004

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Ginkgo biloba, the ginkgo tree, is the oldest living tree, with a long history of use in traditional Chinese medicine. In recent years, the leaf extracts have been widely sold as phytomedicine in Europe and as a dietary supplement worldwide. Effects of Ginkgo biloba extracts have been postulated to include improvement of memory, increased blood circulation, as well as beneficial effects to sufferers of Alzheimer's disease. The most unique components of the extracts are the terpene trilactones, that is, ginkgolides and bilobalide. These structurally complex molecules have been attractive targets for total synthesis. Terpene trilactones are believed to be partly responsible for the neuromodulatory properties of Ginkgo biloba extracts, and several biological effects of the terpene trilactones have been discovered in recent years, making them attractive pharmacological tools that could provide insight into the effects of Ginkgo biloba extracts.

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Chemie der Ginkgolide, I. 10‐Acetyl‐1‐methoxycarbonyl‐2,3,14,15,16‐pentanorginkgolid A, ein Zwischenprodukt zur Herstellung von Bilobalid

Abstract: Die Titelverbindung 8 b, ein Zwischenprodukt der beabsichtigten Partialsynthese von Bilobalid (lo), wird durch Abbau von Ginkgolid A (1) gewonnen. Durch Rontgenstrukturanalyse von 14,15,16-Trinorginkgolid A (7) wird die Struktur der Ringe B-E der Ginkgolide bestatigt.

Cited by 17 publications

References 5 publications

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

Natural antagonists of platelet‐activating factor

Chemistry and Biology of Terpene Trilactones fromGinkgo Biloba

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