Photochemical Approaches to the Bilobalide Core

Emsermann, Jens; Opatz, Till

doi:10.1002/ejoc.201700461

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…A similar, albeit internal, acetal was reported recently as an intermediate in an approach towards the synthesis of bilobalide and survived a strongly acidic, oxidizing step (CrO 3 , H 2 SO 4 , acetone). 73 Our attempts to deprotect or epimerize the oxetane acetals 36 and 37 led to recovery of starting material, and caused us to investigate their unusual persistence.…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…Indeed, substituents at this position impair coordination to the carbonyl group and may have therefore been avoided . Still, there is a continuing interest in the formation of cyclobutanes with a high degree of substitution, and Figure depicts three representative products, rac - 1 , rac - 2 , and rac - 3 , from the recent literature that were prepared by intramolecular [2 + 2] photocycloaddition reactions. One of the few cyclobutanes obtained in enantiomercally enriched form from an α-substituted enone is dihydroquinolone 4 .…”

mentioning

confidence: 99%

Visible-Light-Mediated Enantioselective Photoreactions of 3-Alkylquinolones with 4-O-Tethered Alkenes and Allenes

Jandl

Bach

2020

Org. Lett.

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The title compounds undergo intramolecular [2 + 2] photocycloaddition reactions when irradiated with visible light in the presence of a chiral sensitizer. Up to four defined stereogenic centers are formed in a single step (14 examples with a tethered alkene, 6 examples with an allene, 72–99% yield, 81–99% ee) at catalyst loadings as low as 0.5 mol %. The alkyl group in the 3-position is crucial for the success of the reaction as it leads to a significant decrease of the triplet energy.

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“…The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/molecules28114279/s1, materials and methods [44][45][46], catalyst synthesis methods [47][48][49][50][51][52], experimental procedures, characterization data, 1 H, 13 C and 19 F NMR spectra, HRMS spectrometry data and HPLC chromatogram.…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…13 C NMR (101 MHz, CDCl 3 ) δ: 173.89, 173.75, 173 46,. 173.08, 158.23, 157.50, 148.90, 148.64, 139.37, 139.09, 137.00, 136.83, 133.39, 133.33, 133.27, 132.55, 131.90, 131.63, 130.98, 130.89, 129.39, 129.26, 128.97, 128.88, 128.81, 128.70, 128.50, 128.46, 128.41, 128.37, 128.17, 127.93, 127.75, 127.68, 127.60, 126.27, 126.03, 125.39, 125.26, 124.66, 123.88, 120.09, 119.94, 103.70, 103.63, 61.50, 57.14, 44.95, 43.55, 41.28, 40.04, 31.10, 30.07, 29.81, 29.70, 21.68, 21.65.…”

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confidence: 99%

Desymmetrization of Prochiral N-Pyrazolyl Maleimides via Organocatalyzed Asymmetric Michael Addition with Pyrazolones: Construction of Tri-N-Heterocyclic Scaffolds Bearing Both Central and Axial Chirality

Geng

Hao

et al. 2023

Molecules

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The desymmetrization of N-pyrazolyl maleimides was realized through an asymmetric Michael addition by using pyrazolones under mild conditions, leading to the formation of a tri-N-heterocyclic pyrazole–succinimide–pyrazolone assembly in high yields with excellent enantioselectivities (up to 99% yield, up to 99% ee). The use of a quinine-derived thiourea catalyst was essential for achieving stereocontrol of the vicinal quaternary–tertiary stereocenters together with the C–N chiral axis. Salient features of this protocol included a broad substrate scope, atom economy, mild conditions and simple operation. Moreover, a gram-scale experiment and derivatization of the product further illustrated the practicability and potential application value of this methodology.

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Photochemical Approaches to the Bilobalide Core

Cited by 7 publications

References 36 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

Visible-Light-Mediated Enantioselective Photoreactions of 3-Alkylquinolones with 4-O-Tethered Alkenes and Allenes

Desymmetrization of Prochiral N-Pyrazolyl Maleimides via Organocatalyzed Asymmetric Michael Addition with Pyrazolones: Construction of Tri-N-Heterocyclic Scaffolds Bearing Both Central and Axial Chirality

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