Novel approaches to the asymmetric synthesis of indole alkaloids

The tetracyclic system (219) shares the same heterocyclic skeleton as a plethora of highly bioactive indole alkaloids, exemplified by ajmalicine (161) and deplancheine (204). [Illustration omitted.] Building on earlier work from our research group we recognised that a suitably substituted bicyclic lactam (266) could act as a precursor in an intramolecular N-acyliminium mediated cyclisation leading to targets such as (219). [Illustration omitted.] Methodology has been developed to remove the chiral auxiliary group. Manipulation of the template (219) has allowed us to achieve a novel total synthesis of deplancheine (208) and provided valuable insight for a future asymmetric synthesis of (204).