Mechanisms and Dynamics of Synthetic and Biosynthetic Formation of Delitschiapyrones: Solvent Control of Ambimodal Periselectivity

The mechanism and dynamics for the formation of the delitschiapyrone family of natural products are studied by density functional theory (DFT) calculations and quasiclassical molecular dynamics simulations with DFT and xTB. In the uncatalyzed reaction, delitschiapyrones A and B are formed by Diels-Alder reactions through a single transition state and a post-transition state bifurcation that favors formation of delitschiapyrone B. In water and most likely in the enzyme, the acidic hydroxyquinone ionizes, and the resulting conjugate base undergoes cycloaddition preferentially to delitschiapyrone A. We demonstrate a new type of biosynthetic transformation and variable selectivity from a (4 + 2)/(4 + 3) ambimodal transition state.

Automated summary

The study investigates the mechanism and dynamics of the formation of the delitschiapyrone family of natural products. It is found that under different conditions, different reaction pathways occur, and the presence of enzymes may lead to changes in product selectivity.