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

Abstract

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.

Antiproliferative effect of benzophenones and their influence on cathepsin activity

“…The planarity of the bridge carbonyl and phenyl groups also plays a key role in the orientation of the hydrophobic moieties of the enzymes and inhibitors (Martins et al, 2008a). The torsional angle between the bridge carbonyl group and the least-square plane through aromatic ring is 37.3(7)º for 7-epiclusianone and and 43.7(3)º for garciniaphenone (Martins et al, 2008b). As can be seen from Fig.…”

“…Both compounds were purifi ed as yellow crystalline solids with melting points of 105-107 ºC and 92-93 ºC, and purities of 98.60% and 99.85%, respectively (Santos et al, 1998;Derogis et al, 2008;Martins et al, 2008b). The antiproliferative activity assay results of garciniaphenone and 7-epiclusianone against the human cell lines are shown in Fig.…”

“…The pericarp hexane extract was chromatographed on a silica gel column and eluted with mixtures of n-hexane/ethyl-acetate and ethyl-acetate/ethanol of increasing polarity to obtain the two compounds as described previously (Santos et al, 1998;Derogis et al, 2008;Martins et al, 2008b). The structures were identifi ed as the polyprenylated benzophenone 7-epiclusianone [(1R,5R,7R)-3-benzoyl-4-hydroxy-8,8-dimethyl-1,5,7-tris(3-methylbut-2en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione] (Santos et al, 1998) and garciniaphenone [(1R,5R,7R)-3-benzoyl-4hydroxy-8,8-dimethyl-1,7-bis(3-methylbut-2-en-1-yl) bicyclo[3.3.1]non-3-ene-2,9-dione] (Derogis et al, 2008) ( Fig.…”

“…The structures were identifi ed as the polyprenylated benzophenone 7-epiclusianone [(1R,5R,7R)-3-benzoyl-4-hydroxy-8,8-dimethyl-1,5,7-tris(3-methylbut-2en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione] (Santos et al, 1998) and garciniaphenone [(1R,5R,7R)-3-benzoyl-4hydroxy-8,8-dimethyl-1,7-bis(3-methylbut-2-en-1-yl) bicyclo[3.3.1]non-3-ene-2,9-dione] (Derogis et al, 2008) ( Fig. 1) using IR, UV, MS and NMR spectroscopy, and their molecular geometries established using single crystal x-ray diffraction (XRD) analysis (Santos et al, 1998;Derogis et al, 2008;Martins et al, 2008b).…”

Natural Products as Cathepsin Inhibitors

“…Martins et al have published a study which describes the in vitro inhibitory activity of three natural products isolated from Garcinia brasiliensis against different cysteine and serine proteases, including cathepsin B and cathepsin G, respectively [61], namely guttiferone A, 7-epiclusianone, and garciniaphenone ( Fig. These natural polyprenylated benzophenones were isolated from the ethanolic and hexanic extracts of G. brasiliensis dried and powdered seeds and fruits, as it has been previously reported by them [62][63][64] and were tested for their potential to inhibit papain, trypsin, and cathepsins B and G by spectrofluorometric measurements. These natural polyprenylated benzophenones were isolated from the ethanolic and hexanic extracts of G. brasiliensis dried and powdered seeds and fruits, as it has been previously reported by them [62][63][64] and were tested for their potential to inhibit papain, trypsin, and cathepsins B and G by spectrofluorometric measurements.…”