Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers Tohru Fukuyama • Chemistry Professor at University of Tokyo in Japan – Graduate school of Pharmaceutical Sciences – Synthetic Natural Products chemistry • Discovered Fukuyama Coupling in 1998 Fukuyama Coupling • Coupling between a thioester and an organozinc halide in the presence of a palladium catalyst. – Mild reaction conditions – High chemoselectivity – Less toxic reagents – Stops at ketone (+)-Lyconadin A – Cytotoxic to murine lymphoma L1210 cells and KB cells. – Enhances mRNA expression for nerve growth factor in astrocytoma cells. – Found in Lycopodium complanatum. Lycopodium complanatum (AKA. Northern Ground Cedar) • Club Moss family • Ground level creeping evergreen found in acidic soils of wooded areas and rocky slopes in North America and Europe. • Previously used to make a medicinal tea which would increase urine production, stimulate menstrual flow, and relieve spasms. Retrosynthetic Analysis Lab D-A Ring expansion Forward Synthesis DA Reductive amin aza -prins Dibromo cyclo prop Ring expansion Treatment of 11 with diphenyl disulfide Vinylogous pummer Treatment of 11 with isoamyl nitrite Michael •8.1% overall yield by nitrosoalkene method. •11.6% overall yield by sulfide method.