UC Berkeley

This dissertation discusses our gallium(III)-catalyzed cycloisomerization approach toward the hetidine and hetisine-type diterpenoid alkaloids. The first chapter presents the background of the gallium(III)-catalyzed cycloisomerization reaction. The initial reports for the skeletal rearrangements of 1,6-enyned will be presented and the expansion of the substrate scope to include indenyl alkynes to provide cycloheptadiene products will be discussed. The chapter will conclude with the application of the indenyl alkyne cycloisomerization reaction to the synthesis of several icetexane diterpenoids.

The second chapter focuses on the structure and classification of the C20- diterpenoid alkaloids. The biological activity of selected alkaloids will be discussed. Several approached toward the hetidine and hetisine cores will also be presented along with the two completed total syntheses of the hetisine-type diterpenoid alkaloid nominine.

Chapter three presents our approach toward the hetidine core using the gallium(III)- catalyzed cycloisomerization strategy. Our retrosynthetic analysis of a key-intermediate resembling the hetidine core, that we proposed could be used to access both hetidine and hetisine-type natural products, will be discussed. Synthesis of the cycloisomerization substrate will be presented along with the elaboration of the resulting cycloheptadiene to an intermediate similar to that used by Gin and Peese in their synthesis of nominine. Finally, an oxidative dearomatization approach toward the [2.2.2] bicycle and completion of the hetidine core will be presented.

The final chapter discusses the elaboration of the hetidine core to dihydronavirine A in an attempt to access the hetidine-type natural product navirine A. An interesting C-C bond cleaving reaction, which provides the atisine core from the hetidine core, was also explored.