Enantioselective total synthesis of lycoposerramine congeners through late-stage nitrogen deletion.

Abstract

Lycopodium alkaloids are attractive synthetic targets due to their diverse and unusual skeletal features. While numerous synthetic approaches have been reported, there still remain outstanding synthetic challenges to several lycopodium alkaloids. Herein, a concise total synthesis of lycoposerramine congeners is accomplished through the use of nitrogen deletion strategy (N-deletion) to combine two fully elaborated piperidine and tetrahydroquinoline fragments. Specifically, two natural congeners, lycoposerramine V and W, previously accessible only in 18-23 steps, are each synthesized in 10 steps or less. In contrast to the successful use of N-deletion, many C-C bond forming reactions surveyed fail to deliver the desired coupling product. To further highlight its modular nature, the strategy is applied in the synthesis of two unnatural epimers of lycoposerramine V and W. This work demonstrates the benefits of incorporating modern synthetic methodologies in streamlining access to complex molecules.