Pharmacognosy, Phytochemistry & Natural Products

Biography

Biography: J F F Weber

Abstract

Oligostilbenes are natural polyphenols deriving from the condensation of oxygenated E-stilbene units. Given the number of reactive centres, a large number of oligomeric species have been described, from dimers to octamers. These compounds display significant biological activities, such as antioxidant, anti-inflammatory, antimicrobial properties as well as significant cytotoxicity. Their distribution is restricted to a few families only, including the Dipterocarpaceae (dominant timber trees in Southeast Asia). In these plants, oligostilbenes derive solely from resveratrol. Over the last decade, we undertook to investigate in detail the chemistry of chengal (Neobalanocarpus heimii), one of the most valuable members of this family. Using semi-automated HPLC-based isolation procedures, eighteen compounds including two new dimers (heimiols A & B) and three new tetramers (heimiols C-E) were isolated and their structures elucidated by conventional spectroscopic analysis, including 2D NMR. Eventually, we devised a dereplication approach solely based on MSn using a 3D ion trap mass spectrometer. This method has the advantage of eliminating the dependence on chromatographic data and thus improves its portability. We were able to clearly discriminate tetrameric diastereoisomers differing by a single stereocentre. This approach was used for dereplicating the leaf and bark extracts of that tree species. In order to better understand the oligostilbenes biogenesis, we examined their biomimetic synthesis. Using one-electron oxidants we were able to obtain dimers in a regio- and stereoselective manner. Upon varying the metal oxidant (AgOAc, CuBr2, FeCl3.6H2O, FeCl3.6H2O/NaI, PbO2, VOF3), the solvent (over the whole range of polarities), and the oxygenated substitution pattern of the starting material, stilbenoid oligomers with totally different carbon skeletons were obtained. By looking at these results combined with all those from the literature, we could explain the determinism of the type of skeleton produced with the aid of hard and soft acid/base concepts in conjunction with stable noncovalent π stacking of the stilbene precursors. Quantum mechanics (density functional theory, DFT) provided much support to this theory and further hinted at a radical-neutral mechanism against the conventional wisdom. We further considered the formation of tetrameric species and were able to explain their stereochemistry from specific -stacking of -viniferin precursor units. Again, DFT modeling supported our hypotheses.