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

Sonogashira Coupling

Eschenmoser-Tanabe Fragmnetation

Oxidation

cyclization

Synthesis of “starting material”

32% 77%, 87% ee

9, 44%, 99% 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