DFT Study on the Biosynthesis of Asperterpenol and Preasperterpenoid Sesterterpenoids: Exclusion of Secondary Carbocation Intermediates and Origin of Structural Diversification.

The biosynthetic pathway to asperterpenol, a sesterterpenoid featuring a 6/6/8/5 tetracyclic ring system, was proposed to involve three secondary (2°) carbocation intermediates ( B , D , and I ), but it remains controversial whether or not these are viable. Further, the proposed 11/6/5 tricyclic intermediate C has the same "ChemDraw" structure as an intermediate in the biosynthesis of preasperterpenoid, which has a very different 5/7/(3)6/5 pentacyclic skeleton. Here, we present a detailed scrutiny of the asperterpenol/preasperterpenoid biosynthetic pathways based on comprehensive DFT calculations.