Mapping Out Biogenetic Hypotheses by Chemical Synthesis

Synthesis of natural products via their postulated or established biosynthetic intermediates ('biomimetic synthesis' or 'bio-inspired synthesis') has the power to identify both yet undiscovered intermediates and undiscovered mechanistic pathways for their formation. In this account, we report on our recent studies on unusual hypotheses for biosynthetic transformations, such as a late-stage aldol reaction (periconianone A), benzilic acid rearrangement (taiwaniaquinone H), a redox-neutral light-driven C–H activation (taiwaniaquinol A and cyclocoulterone), a hetero Diels-Alder reaction (obtusinones), aziridinium chemistry (Securinega alkaloids), and a [3+2] nitrone olefin cycloaddition (virosaine A). All these studies provided evidence on the molecular level for the feasibility of these transformations, and suggest that further studies investigating the relevance of these hypotheses in biological systems are warranted.