concise total synthesis of (+)-lyconadin a
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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