Biomimetic drug development: towards the oxidative variation of polycyclic carbon skeletons

In this work we report an efficient synthetic strategy, inspired by the biogenesis of biologically active terpenoid natural products. Through the use of a novel (4+3)– cycloaddition and subsequent oxidative variation of the polycyclic reaction products, incorporating a fused furan and seven membered ring, a small collection of compounds with interesting “drug lead”-like structures and properties was prepared. These results show that a library of “metabolites” of unnatural polycyclic scaffolds could be prepared in a very short amount of time, which might be very useful as chemical probes for studying various biological processes and for use in various drug discovery screening assays.