Biosynthesis and Conformational Properties of the Irregular Sesquiterpenoids Isothapsadiene and β‑Isothapsenol

A carbocation cyclization/rearrangement
mechanism for the biosynthesis
of isothapsadiene and β-isothapsenol is shown to be energetically
viable on the basis of density functional theory (DFT) calculations.
In addition, for both isothapsadiene and β-isothapsenol, variable-temperature
NMR experiments reveal two equilibrium conformers that undergo hindered
exchange. The identities of these conformers, which are related by
a chair-flip, are confirmed by DFT calculations on their structures,
energies, 1H and 13C chemical shifts, and interconversion
pathways.