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Divergent Diels–Alder Reactions in the Biosynthesis and Synthesis of Endiandric-Type Tetracycles: A Computational Study
- Kron, Kareesa J., Kosich, Mikaela, Cave, Robert J., Vosburg, David A.
- Journal of organic chemistry 2018 v.83 no.18 pp. 10941-10947
- biosynthesis, cycloaddition reactions, density functional theory, moieties, polyketides
- Endiandric acids and related polyketide natural products arise from polyene precursors and occur naturally as fused and bridged tetracycles. In some cases, the intramolecular Diels–Alder reactions that produce fused and bridged tetracycles result from a diene tether that may act as either a 4π or 2π component in the cycloaddition. To examine the preference for fused or bridged products, we applied density functional theory (using the M06-2X and B3LYP functionals) to reactants with various substituents for both fused and bridged transition states. Fused products were generally preferred except when disfavored by extreme steric hindrance (e.g., a tert-butyl group). These computational results are consistent with experimental data and suggest the existence of as-yet undiscovered natural products.