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 Ring expansion

D-A

Forward Synthesis

DA

Reductiveamin

aza -prins

Dibromo cyclo prop

Ringexpansion

Treatment of 11 with diphenyl disulfide

Vinylogouspummer

Treatment of 11 with isoamyl nitrite

•8.1% overall yield by nitrosoalkene method.•11.6% overall yield by sulfide method.

Michael