Selective C‐6 Prenylation of Flavonoids <i>via</i> Europium(III)‐ Catalyzed Claisen Rearrangement and Cross‐Metathesis

Tischer, Sandra; Metz, Peter

doi:10.1002/adsc.200600454

Cited by 45 publications

(28 citation statements)

References 49 publications

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“…The 7-O-allylated naringenin derivative 5 was formed as a byproduct of a Mitsunobu reaction with allyl alcohol. After Claisen rearrangement of the major product 4 [11] and subsequent deprotection 6-allylnaringenin (6) resulted. 6-Propylnaringenin (7) was generated by hydrogenation of compound 6.…”

Section: Set Of Compoundsmentioning

confidence: 99%

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

Lättig

Böhl

Fischer

et al. 2007

J Comput Aided Mol Des

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The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

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Section: Set Of Compoundsmentioning

confidence: 99%

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

Lättig

Böhl

Fischer

et al. 2007

J Comput Aided Mol Des

Self Cite

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“…[1][2][3] Due to the broad pharmacological activities of prenylated flavonoids, various strategies have been developed for their regioselective chemical synthesis, especially for C-prenylated derivatives. [4,5] Meanwhile, significant progress has also been made in the identification of enzymes that catalyze the transfer of prenyl moieties onto the flavonoid skeleton. [6] Three membrane-bound prenyltransferases from Sophora flavescens have been cloned, expressed, and characterized biochemically.…”

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confidence: 99%

Prenylation of Flavonoids by Using a Dimethylallyltryptophan Synthase, 7‐DMATS, from Aspergillus fumigatus

2011

ChemBioChem

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Production of typical plant metabolites by a fungal enzyme: Fungal prenyltransferases of the DMATS superfamily are mainly involved in the biosynthesis of prenylated indole alkaloids, but also catalyze the prenylation of tyrosine and naphthalene derivatives. In this study, nine prenylated flavonoids were produced by using the recombinant dimethylallyltryptophan synthase 7-DMATS from Aspergillus fumigatus.

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“…Two approaches towards the prenylcoumarin motif are distinguished: (1) starting from salicylic aldehydes and cinnamates through the tandem Claisen rearrangement/Wittig olefination/cyclization sequence [9] and (2) using preformed coumarin skeleton via the Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis reaction sequence [10]. The latter was used by Tischer and Metz for the synthesis of the naturally occurring 8-prenylnaringenin (1), 6-prenylnaringenin (4), 6-prenylgenistein (5), and 6-prenylquercetin (6) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Assembling the prenylneoflavone system through a Pechmann condensation/Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis sequence

et al. 2020

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The multistep synthesis of a prenylneoflavone through a sequence of the Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis reaction has been accomplished in 5% yield over six steps starting from commercially available 3-methoxyacetophenone. The sequence is shown to be compatible with a Pechmann condensation which proved to be a robust and cost-effective method for the assembling of the α-pyrone core. The results open doors to a general approach to the prenylneoflavone system starting from phenol and acetophenone derivatives. Graphic abstract

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Selective C‐6 Prenylation of Flavonoids via Europium(III)‐ Catalyzed Claisen Rearrangement and Cross‐Metathesis

Cited by 45 publications

References 49 publications

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

Prenylation of Flavonoids by Using a Dimethylallyltryptophan Synthase, 7‐DMATS, from Aspergillus fumigatus

Assembling the prenylneoflavone system through a Pechmann condensation/Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis sequence

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