1. Total Synthesis of: (-) Mersicarpine
Research: Tohru Fukuyama
Presentation: Carl Brothers

2. Tohru Fukuyama Chemistry Professor at University of Tokyo in Japan
Graduate school of Pharmaceutical Sciences
Synthetic Natural Products chemistry
Discovered Fukuyama Coupling in 1998

3. 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

4. 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.

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

6. Retrosynthetic Analysis
Oxidation
cyclization
Sonogashira Coupling
Eschenmoser-Tanabe Fragmnetation

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

8. Total Synthesis
72%
87%

9. 88%
60%

10. 87%
78%
78%

11. 97%
76%
96%, 1.34% from cyclohexanone
42 mg of final product