Synthetic Studies Towards the Preparation of 2‐Benzyl‐2‐ hydroxybenzofuran‐3(2<i>H</i>)‐one, the Prototype of Naturally Occurring Hydrated Auronols

Löser, Reik; Chlupáčová, Marta; Mareček, Aleš; Opletalová, Veronika; Gütschow, Michael

doi:10.1002/hlca.200490232

Cited by 20 publications

(11 citation statements)

References 18 publications

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“…Alphitonin was obtained by enzymatic transformation of taxifolin followed by purification and structure elucidation by nuclear magnetic resonance (NMR) analysis (11). (Ϯ)-Flavanonol was obtained by oxidation of the corresponding chalcone (1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one) using hydrogen peroxide (20).…”

Section: Chemicals (ϯ)-Taxifolin and (ϯ)mentioning

confidence: 99%

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

et al. 2016

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The enzyme catalyzing the ring-contracting conversion of the flavanonol taxifolin to the auronol alphitonin in the course of flavonoid degradation by the human intestinal anaerobe Eubacterium ramulus was purified and characterized. It stereospecifically catalyzed the isomerization of (؉)-taxifolin but not that of (؊)-taxifolin. The K m for (؉)-taxifolin was 6.4 ؎ 0.8 M, and the V max was 108 ؎ 4 mol min ؊1 (mg protein) ؊1 . The enzyme also isomerized (؉)-dihydrokaempferol, another flavanonol, to maesopsin. Inspection of the encoding gene revealed its complete identity to that of the gene encoding chalcone isomerase (CHI) from E. ramulus. Based on the reported X-ray crystal structure of CHI (M. Gall et al., Angew Chem Int Ed 53:1439 -1442, 2014, http://dx.doi.org/10.1002/anie.201306952), docking experiments suggest the substrate binding mode of flavanonols and their stereospecific conversion. Mutation of the active-site histidine (His33) to alanine led to a complete loss of flavanonol isomerization by CHI, which indicates that His33 is also essential for this activity. His33 is proposed to mediate the stereospecific abstraction of a proton from the hydroxymethylene carbon of the flavanonol C-ring followed by ring opening and recyclization. A flavanonol-isomerizing enzyme was also identified in the flavonoid-converting bacterium Flavonifractor plautii based on its 50% sequence identity to the CHI from E. ramulus. IMPORTANCE Chalcone isomerase was known to be involved in flavone/flavanone conversion by the human intestinal bacterium E. ramulus.Here we demonstrate that this enzyme moreover catalyzes a key step in the breakdown of flavonols/flavanonols. Thus, a single isomerase plays a dual role in the bacterial conversion of dietary bioactive flavonoids. The identification of a corresponding enzyme in the human intestinal bacterium F. plautii suggests a more widespread occurrence of this isomerase in flavonoid-degrading bacteria. F lavonoids represent a major group of plant-derived polyphenolic compounds and have been implicated in beneficial effects on human health (1-4). The flavonoids are classified into several subgroups, which include, among others, flavonols, flavanonols, flavones, flavanones, and chalcones. Quercetin (Fig. 1) is a highly abundant dietary flavonoid that shows a broad range of biological activities. Thus, this flavonol has been intensively studied with respect to its role in disease prevention and use in therapy (5-7). The effects of quercetin and other flavonoids depend on how they are metabolized in the human body, including their conversion by intestinal bacteria (8). Beside deglycosylation and deconjugation, intestinal bacteria are also able to further transform the resulting flavonoid aglycones. However, knowledge about the corresponding bacterial species and, in particular, the enzymes involved is still limited.Eubacterium ramulus and Flavonifractor plautii (formerly Clostridium orbiscindens) are human intestinal bacteria that have been demonstrated to cleave the central heterocyc...

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Section: Chemicals (ϯ)-Taxifolin and (ϯ)mentioning

confidence: 99%

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

et al. 2016

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“…The 13 C NMR signals at 182.7 and 149.4 ppm, assigned to carbons 5a and 10a, respectively (see Table S2, Supporting Information), permit us to conclude that the furan ring is stable and does not undergo ring opening reaction under these conditions (see below). 27,28…”

Section: Results and Discussionmentioning

confidence: 99%

pH-Dependent Multistate System Generated by a Synthetic Furanoflavylium Compound: An Ancestor of the Anthocyanin Multistate of Chemical Species

2019

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The multistate of chemical species generated by 4′-hydroxy-3,2′-furanoflavylium is similar to that of anthocyanins and related compounds. This furanoflavylium multistate system was fully characterized by UV–visible and NMR spectroscopy, allowing determination of the respective equilibrium and rate constants. In contrast to the multistate generated by flavylium cations derived from anthocyanins and related compounds, the furanoflavylium multistate is characterized by much slower hydration and tautomerization (pyran ring opening–closing). In addition, the cis–trans isomerization of the chalcones of this system (2′-hydroxyaurones) is extremely slow when compared with anthocyanins. The observed similar order of magnitude for tautomerization and isomerization rate constants leads to peculiar kinetics from the flavylium cation (pH = 1) to the stable trans -chalcone (higher pH values). The hemiketal appears and disappears during the first stages of the kinetics, which gives the intermediate cis -chalcone (pseudo-equilibrium). This last species disappears in a much slower process, as fully characterized by 1 H NMR, to give the final trans -chalcone.

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“…In contrast to the oxidation of 2-benzylidenebenzofuran-3(2H)-one, which easily afforded the unsubstituted III upon treatment with H 2 O 2 and Triton B (benzyl trimethylammonium hydroxide) [10,11], the preparation of the tetramethoxy substituted epoxide III (R = R' = OMe, R'' = 3,4-(OMe) 2 ) turned out to be difficult.…”

Section: Introductionmentioning

confidence: 94%

“…The auronol alphitonin has been identified as a metabolite of the quercetin degradation by the anaerobic human intestinal bacterium Eubacterium ramulus [9]. To prepare auronols of type IV, the epoxide III (R = R' = R'' = H) was successfully transformed with H 2 in the presence of Pd/C in toluene at -25 to -20° to obtain IV (R = R' = R'' = H), the prototype of naturally occurring auronols [10]. In a further attempt, we planned to prepare the tetramethoxy substituted epoxide III (R = R' = OMe, R'' = 3,4-(OMe) 2 ).…”

Section: Introductionmentioning

confidence: 99%

Darzens reaction of 2‐bromo‐4,6‐dimethoxy‐3(2H)‐benzofuranone with aromatic aldehydes to form flavonoids

Ottersbach

Bolek

Lepičová

et al. 2008

Journal of Heterocyclic Chem

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The applicability of 2-bromo-4,6-dimethoxy-3(2H)-benzofuranone (1) to produce flavonoid-derived epoxides in the course of the Darzens reaction with aldehydes was investigated. However, instead of the epoxides, flavonols 3 and, in certain cases, benzofuranyl-substituted flavonols 4 were isolated. The generation of 3 is assumed due to a ring expansion of the initially formed epoxides. These flavonols can react with 1 to produce the unexpected 1:2 adducts 4 as minor products. The structure of the hexamethoxy derivative 4b (R 1 = H, R 2 = R 3 = OMe) was confirmed by X-ray crystallographic analysis.

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Synthetic Studies Towards the Preparation of 2‐Benzyl‐2‐ hydroxybenzofuran‐3(2H)‐one, the Prototype of Naturally Occurring Hydrated Auronols

Cited by 20 publications

References 18 publications

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

pH-Dependent Multistate System Generated by a Synthetic Furanoflavylium Compound: An Ancestor of the Anthocyanin Multistate of Chemical Species

Darzens reaction of 2‐bromo‐4,6‐dimethoxy‐3(2H)‐benzofuranone with aromatic aldehydes to form flavonoids

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