Total Synthesis of: (-) Mersicarpine Research: Tohru Fukuyama Presentation: 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

Mersicarpine Found in the stem-bark extract of the Malayan K. arborea. Also found in other Kopsia. A small tree with waxy leaves, white flowers, and dark fruit. Found in lowland rainforests and beach forests close to the sea throuought southeast Asia and parts of Australia.

Mersicarpine Indole alkaloid. Biological activity? Medicinal uses? Similar compounds show anti- cancer and anti- HIV activity.

Retrosynthetic Analysis Oxidation cyclization Sonogashira Coupling Eschenmoser-Tanabe Fragmnetation

Synthesis of “starting material” 32% 77%, 87% ee Semicarbazide hydrochloride, sodium acetate, ethanol 9, 44%, 99% ee 0 C, 24 h

Total Synthesis 72% 87%

88% 60%

87% 78% 78%

97% 76% 96%, 1.34% from cyclohexanone 42 mg of final product