Natural polyprenylated benzophenones: keto-enol tautomerism and stereochemistry

Martins, Felipe Terra; Cruz, José W. da; Derogis, Priscilla Bento Matos Cruz; Santos, Marcelo H. dos; Veloso, Márcia Paranho; Ellena, Javier; Doriguetto, Antônio C.

doi:10.1590/s0103-50532007000800011

Cited by 29 publications

(18 citation statements)

References 18 publications

(35 reference statements)

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“…The two other compounds, 7-epiclusianone (2; Scheme) [18] and guttiferone A [8], have already been extracted from other plants of the same family and can also be obtained from G. brasiliensis seeds. In contrast to guttiferone A, which is found only in the seeds (isolated from the EtOH extract, see [20]), compound 2 constitutes the major secondary metabolite extracted from the fruits of this species. The crystal structures of compound 2 [18] and guttiferone A [19] [20] are known.…”

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confidence: 89%

“…Table 4), distorts the C(3)ÀC(10) bond towards the centroid of the chelate ring. As expected for this independent displacement, it does not influence the O(2)ÀC(10)ÀC (3) angle (119.0(3)8 for 1 vs. an average of 119(2)8 for 161 1-like entries in the CSD), whereas In guttiferone A, a benzophenone structurally related to compound 1, which carries a 3-(3,4-dihydroxybenzoyl) instead of the 3-benzoyl group, and which is present in the G. brasiliensis seeds, the OH group in 4-position of the aromatic ring allows a further electron delocalization within the 4-HOÀC 6 H 3 (OH)ÀC(11)ÀC(10)ÀO(2) moiety that enhances the electron density at O(2) [20]. Thus, O(2) rather than O(1) is covalently bonded to the H-atom, and the keto -enol tautomer with the C(10)ÀO(2)ÀH/C(4)¼O(1) structure was found to contribute most to the solid state of guttiferone A, in contrast to the prevailant tautomer with the C(10)¼O(2)/ C(4)ÀO(1)ÀH moiety determined here in the crystal structure of 1.…”

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confidence: 99%

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Crystal Structure of Garciniaphenone and Evidences on the Relationship between Keto–Enol Tautomerism and Configuration

Martins

Camps

Santos

et al. 2008

Helvetica Chimica Acta

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Garciniaphenone (=rel‐(1R,5R,7R)‐3‐benzoyl‐4‐hydroxy‐8,8‐dimethyl‐1,7‐bis(3‐methylbut‐2‐en‐1‐yl)bicyclo[3.3.1]non‐3‐ene‐2,9‐dione; 1), a novel natural product, was isolated from a hexane extract of Garcinia brasiliensis fruits. The crystal structure of 1 as well as the selected geometrical and configurational features were compared with those of known related polyprenylated benzophenones. Garciniaphenone is the first representative of polyprenylated benzophenones without a prenyl substituent at C(5). Notably, the absence of a 5‐prenyl substituent has an impact on the molecular geometry. The tautomeric form of 1 in the solid state was readily established by a residual‐electronic‐density map generated by means of a difference Fourier analysis, and there is an entirely delocalized six‐membered chelate ring encompassing the keto–enol moiety. The configuration at C(7) was used to rationalize the nature of the keto–enol tautomeric form within 1. The intermolecular array in the network is maintained by nonclassical intermolecular H‐bonds.

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confidence: 89%

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confidence: 99%

Crystal Structure of Garciniaphenone and Evidences on the Relationship between Keto–Enol Tautomerism and Configuration

Martins

Camps

Santos

et al. 2008

Helvetica Chimica Acta

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“…The carbonyl group in positions 2 and 10 can establish tautomerism equilibrium with the adjacent hydroxyl group in position 4 (Scheme 1). This was described by Martins et al [33], who say that the tautomers of Gutifferone in general exist in a solution in a condition of equilibrium. The position of the tautomerism equilibrium K 1 depends critically on the pH of the medium.…”

Section: Resultsmentioning

confidence: 93%

Voltammetry Study of an Anti-HIV Compound by means of a Thin Organic Membrane

Nassi

Ebelle

Manga

et al. 2013

International Journal of Electrochemistry

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Cyclic and square wave voltammetries have been used to study electrochemical behaviour of an anti-HIV agent (Guttiferone A) at the liquid-liquid interface. The thin organic membrane is formed by an organic solvent containing redox probe. Guttiferone A, a benzophenone (BP) with appropriate electrolyte. It is demonstrated that BP possesses three reduction systems due to the redox transformation of the three tautomeric forms that lead to the migration of proton between the hydroxyl group in position 4 and the carbonyl group in positions 2 and 10. The transfer of proton from the aqueous solution to the organic phase is crucial for the redox transformation of BP into the organic membrane. The voltammograms obtained are strongly influenced by the pH of the aqueous phase. The electrochemical mechanism consists of 2e − /2H + exchange to form the separate redox compound BPH 2 .

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“…28,29 Several studies have shown the efficacy of triazole as potent elastase inhibitors. 30 Our research group has been involved in investigating several synthetic [33][34][35][36][37] and natural 38 benzophenones. For instance, the anti-inflammatory potential of 2,2',4-trihydroxybenzophenone was assessed by means of the rat-paw-edema induced by carrageenan application assay.…”

Section: Introductionmentioning

confidence: 99%

“…The 1,2,3-triazole functionality has gained tremendous interest of numerous researchers, since compounds containing this structural motif exhibits several biological activities, such as antituberculosis, 18 anticancer, Our research group has been involved in investigating several synthetic [33][34][35][36][37] and natural 38 benzophenones. For instance, the anti-inflammatory potential of 2,2',4-trihydroxybenzophenone was assessed by means of the rat-paw-edema induced by carrageenan application assay.…”

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Synthesis of 1,2,3-Triazole Derivatives of 4,4’-Dihydroxybenzophenone and Evaluation of Their Elastase Inhibitory Activity

Dias

Gularte

Teixeira

et al. 2018

J. Braz. Chem. Soc.

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The present investigation describes the synthesis of a series of novel triazole derivatives from 4,4'-dihydroxybenzophenone along with their elastase inhibitory activity. The 1,2,3-triazoles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), also known as click reaction, between bis(4-(prop-2-yn-1-yloxy))benzophenone and several benzyl azides. It was found that five derivatives exhibited significant inhibitory effects, presenting half maximal inhibitory concentration (IC 50 ) values in the range of 16.6 to 72.1 µM. The most active compound, namely bis(4-(1-(4-iodobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)benzophenone (IC 50 = 16.6 ± 1.9 µM), was found to bind to elastase with the inhibition constant (K i ) of 11.12 µM, thereby illustrating competitive inhibitory behavior. Further, docking investigations provided insights on the possible binding mode of the most active compound with the elastase.Keywords: elastase, serine protease, CuAAC reaction, benzophenone, 1,2,3-triazole IntroductionBenzophenones are of chemical, medicinal, and industrial interest.1 Several of their derivatives exhibit important biological activities like anticancer, 2,3 antiviral on HIV, 4 antibacterial, 5 activity against Alzheimer's disease, 6 and anti-inflammatory. 7The anti-inflammatory action of benzophenones is well documented in the literature. 8 For instance, ketoprofen is an example of synthetic benzophenone that has been commercialized as an anti-inflammatory drug. Recently, studies have demonstrated that structural modifications carried out on this drug afforded substances with improved anti-inflammatory activity. 9 Miyano et al. 10 synthesized a series of 4-(acyloxy)benzophenones and 4,4'-bis(acyloxy) benzophenones and evaluated their anti-inflammatory activity using human neutrophil elastase (HNE) as a template. The derivatives 4-(pivaloyloxy)benzophenone and 4-(isobutyryloxy)benzophenone showed elastase inhibitory activity with half maximal inhibitory concentration (IC 50 ) of 0.62 and 0.25 µM, respectively. It was found that 4,4'-bis(acyloxy)benzophenones were more potent than the corresponding 4-(acyloxy)benzophenones, highlighting 4,4'-bis(2,2-dimethylpropanoate)benzophenone with IC 50 = 0.12 µM and inhibition constant (K i ) = 7.1 × 10 -8 M.10 Serine proteases are involved in different branches of the immune system and play an important role in inflammation. In a recent investigation from our research group, Martins et al. 11 reported in vitro inhibition of serine proteases by synthetic and natural benzophenones, which showed moderate to high inhibitory effects against all the enzymes. Guttiferone A displayed IC 50 of 2.7 ± 0.1 µM, a value similar to the IC 50 of chymostatin (2.1 ± 0.1 µM), a classical inhibitor of serine protease cathepsin G. Braz. Chem. Soc. 98 Molecular hybridization has been shown to be a promising strategy for obtaining new compounds. It is mainly based on the combination of two or more known bioactive pharmacophoric fragments, by appropriate fusion, into a sing...

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Natural polyprenylated benzophenones: keto-enol tautomerism and stereochemistry

Cited by 29 publications

References 18 publications

Crystal Structure of Garciniaphenone and Evidences on the Relationship between Keto–Enol Tautomerism and Configuration

Crystal Structure of Garciniaphenone and Evidences on the Relationship between Keto–Enol Tautomerism and Configuration

Voltammetry Study of an Anti-HIV Compound by means of a Thin Organic Membrane

Synthesis of 1,2,3-Triazole Derivatives of 4,4’-Dihydroxybenzophenone and Evaluation of Their Elastase Inhibitory Activity

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