Polycyclic Molecules from Linear Precursors: Stereoselective Synthesis of Clavolonine and Related Complex StructuresFinancial support was provided by the National Institutes of Health (GM 33328-20), Eli Lilly, Merck, and Amgen

At the time of this publication, over 100 lycopodium alkaloids have been isolated. The 16-carbon-atom-containing lycopodium alkaloid family features a variety of polycyclic ring sizes, stereochemistry, and oxidation patterns. The classic tetracyclic skeleton of the lycopodane family has a rich history in organic chemistry and has been a proving ground for new approaches to the synthesis of polycyclic alkaloid targets. Despite the number of research groups that have contributed to the synthesis of this family of alkaloids, all have proceeded in a linear fashion from cyclic starting materials. The structure of lycopodine provides an instructive model to explore a strategy centered on 1) a convergent synthesis of a linear precursor that contains the complete carbon backbone and 2) the incorporation of a reaction cascade sequence to construct the remaining carbon–carbon bonds. In this study, we pursued the synthesis of clavolonine (2), which was