Synthetic Strategies for the Lepadiformines and Cylindricine C via Tandem Schmidt Reactions

Abstract

Marine flora and fauna have provided numerous alluring natural products, some of which contribute to treating diseases. The genus Clavelina is the source of a variety of tricyclic alkaloids, including the lepadiformine and cylindricine families. Novel approaches to synthesizing these molecules are sought after to increase their accessibility and for analogue development. In this dissertation, reaction sequences involving an intramolecular Schmidt transformation, which can quickly build up the molecular architecture associated with these targets is described. In one approach, the Lewis acid promoted intramolecular Schmidt reaction is combined in series with a Prins reaction to afford an interesting tricyclic lactam. This methodology culminates in a formal synthesis of lepadiformine A and a total synthesis of lepadiformine C. In another project, a tandem Diels-Alder/Schmidt reaction is utilized to prepare a similar tricyclic lactam. This process is applied toward an asymmetric total synthesis of (-)-cylindricine C. The preparation for the optically active starting material for the synthesis of (-)-cylindricine C is also discussed, as it is a prominent figure in the preparation of prostaglandins.