Assessing the viability of biosynthetic pathways for calophyline A formation—are pericyclic reactions involved?

The results of quantum chemical calculations on a previously proposed biosynthetic pathway for the formation of calophyline A from rhazimol, which features formally forbidden 4-electron [1,2] and [1,3] sigmatropic shifts, are discussed. The proposed pathway was not found to be energetically viable, despite a surprisingly low predicted barrier for the [1,3] shift, but an alternative route involving a series of tautomerizations and carbonyl addition reactions is shown to be more energetically feasible.