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%
9, 44%, 99% ee
77%,
87% ee
Semicarbazide hydrochloride,
sodium acetate,
ethanol
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