Navigating the Landscape of Cycloartanyl Cations: Synthesis of Fortunefuroic Acid I, Parkeol,...

For the semisynthesis of plant-derived triterpenoid natural products, access to cycloartenol or a derivative is mandatory. We here describe a robust access from the renewable feedstock γ-oryzanol and isolation by differentiable reactivity. Using either radical-polar crossover or polar modes of activation, we then selectively access different carbenium ions and elucidate their fate in rearrangements. As a result, a chemical toolbox for the modular and stepwise skeletal rearrangement to access natural products with increasing levels of divergence from the parent cycloartane is reported. Using this toolbox, parkeol-, 17,13-friedocycloartane-, 17,13-friedoparkeol-, as well as 17,13- and 17,14-friedolanostane systems are selectively obtained and transformed via short routes to the plant metabolites parkeol (3), fortunefuroic acid I (4), 25,26,27-trinor-3α-hydroxy-17,13-friedolanosta-8,12-dien-23-one ("sibiricanone", 5), and spirochensilide A (6). Probing the innate reactivity of cycloartanyl cations and corroborating the experimental results with DFT calculations sheds light on the potential biogenesis of these and related plant metabolites and, thus, can account for the occurrence of 17,14-friedolanostanes in plants.