Abstract:

This presentation will focus on the development of synthetic strategies to facilitate the understanding of the lissoclimide's biological activity and the development of a general synthetic route towards C20-diterpenoid alkaloids. 

The first part of the presentation will describe efforts to reliably synthesize all the desired C2 halogen-bearing lissoclimides and to develop a stereoselective methylation strategy at the C2 position of sclareolide. It concludes by analyzing the biological activity of these lissoclimide analogues against multiple cancer cell lines and by analyzing the X-ray cocrystal structures of these analogues bound to the 80s eukaryotic ribosome. 

The second part of the presentation focuses on our efforts towards the syntheses of hetidine and hetisine-type natural products. This presentation will detail different strategies employed to form the oxetane-bearing AB core of hetidine-type natural products as well as the successful installation of all the carbon atoms within the albiovoline and hetisine framework.