¹⁸O stable isotope labeling, quantitative model experiments, and molecular dynamics simulation studies on the Trans-specific degradation of the bitter tasting Lso-α-acids of beer

The typical bitterness of fresh beer is well-known to decrease in intensity and to change in quality with increasing age. This phenomenon was recently shown to be caused by the conversion of bitter tasting trans-iso-a-acids into lingering and harsh bitter tasting tri- and tetracyclic degradation products such as tricyclocohumol, tricyelocohumene, isotricyclocohumene, tetracyclocohumol, and epitetraeyclocohumol. Interestingly, the formation of these compounds was shown to be trans-specific and the corresponding c/s-iso-α-acids were found to be comparatively stable. Application of ¹⁸O stable isotope labeling as well as quantitative model studies combined with LC - MS/MS experiments, followed by computer-based molecular dynamics simulations revealed for the first time a conclusive mechanism explaining the stereospecific transformation of rrans-iso-α-acids into the tri- and tetracyclic degradation products. This transformation was proposed to be induced by a proton-catalyzed carbon/carbon bond formation between the carbonyl atom C(1′) of the isohexenoyl moiety and the alkene carbon C(2″) of the isoprenyl moiety of the frans-iso-α-acids.