Studies toward a total synthesis of acutumine featuring classical carbonyl reactivity

ORGN 853

Robert J. Moreau, rmoreau@princeton.edu and Erik J. Sorensen, ejs@princeton.edu. Department of Chemistry, Princeton University, Princeton, NJ 08544
Acutumine was isolated from the plant Menispermum dauricum DC in 1929, and its unprecedented chlorine-containing, tetracyclic alkaloid structure, including absolute stereochemistry, was elucidated in 1967 through the application of chemical degradation and X-ray crystallographic methods. In addition to its intriguing architecture, acutumine has also shown promising varied biological activity. It was shown in 2002 that acutumine is a moderately selective inhibitor (IC50 = 13.2 ƒÝM) of human T cell growth in vivo, and animal experimental models revealed in 2003 the memory enhancing properties of acutumine. Our current approach toward a synthesis of acutumine and related structures seeks to rely on classical carbonyl reactivity to rapidly and efficiently access the acutumine architecture from the parent pyrrolidine ring.