Open AccessMechanisms and Dynamics of Synthetic and Biosynthetic Formation of Delitschiapyrones: Solvent Control of Ambimodal Periselectivity
Author(s) -
Yike Zou,
K. N. Houk
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c05293
Subject(s) - chemistry , conjugate , density functional theory , transition state , computational chemistry , molecular dynamics , selectivity , cycloaddition , solvent , transition state theory , solvent effects , concerted reaction , chemical physics , stereochemistry , catalysis , organic chemistry , reaction rate constant , kinetics , physics , mathematical analysis , mathematics , quantum mechanics
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.