New approaches for the asymmetric synthesis of pyrroloisoquinoline and isoquinoline alkaloids

Pyrroloisoquinoline (n = 1) and the pyridoisoquinoline (n = 2) ring systems (2) are found to be the major structural motif of the Erythrina and the protoberberine group of alkaloids, respectively. We have recognised that suitable bicyclic lactams (1) could act as precursors, in an intramolecular N-acyliminium ion-mediated cyclisation, resulting in a stereoselective approach to the core of the Erythrina and protoberberine ring systems. [Illustration omitted.] Access to the tetracyclic core of the Erythrina alkaloids (3) through the application of N-acyliminium ion chemistry is well established within our group. This has been demonstrated in a formal asymmetric synthesis of both enantiomers of the Erythrina alkaloid, 3- demethoxyerythratidinone (4), and described in this thesis. [Illustration omitted.] Our investigations have also involved the manipulation of this methodology toward the synthesis of the Erythrina alkaloid (-)-erysotrine (5) and the protoberberine alkaloid (-)-xylopinine (6).