Studies Toward the Total Synthesis of Bielschowskysin
Townsend, Steven D'wayne
The dissertation contained herein describes the synthetic efforts toward the total synthesis of the furanocembrane bielschowskysin, and comprises five generations of synthetic strategies. Bielschowskysin was isolated in 2004 from P. kallos and was shown to demonstrate antiplasmodial activity against Plasmodium falciparum (IC50 = 10 μg/mL). Additionally, bielschowskysin displayed strong and specific in vitro cytotoxicity against EKVX nonsmall cell lung cancer (GI50 < 0.01 μM) and CAKI-1 renal cancer (GI50 < 0.51 μM) using the NCI’s in vitro antitumor screen. Chapter I highlights the significance of the furanocembranes to the synthetic community. Chapter II examines the initial [2+2] photocycloaddition. Chapter III outlines four generations of strategies toward bielschowskysin and reviews methods to synthesize α-substituted butenolides. Chapter IV describes the chemistry of ynamines and discusses a final synthetic sequence, with the potential to culminate in the total synthesis of bielschowskysin.