Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl...
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Transcript of Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl...
![Page 1: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/1.jpg)
Concise Total Synthesis of (+)-Lyconadin A
Research by: Tohru Fukuyama
Presentation by: Carl Brothers
![Page 2: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/2.jpg)
Tohru Fukuyama
• Chemistry Professor at University of Tokyo in Japan– Graduate school of
Pharmaceutical Sciences– Synthetic Natural Products
chemistry
• Discovered Fukuyama Coupling in 1998
![Page 3: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/3.jpg)
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
![Page 4: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/4.jpg)
(+)-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.
![Page 5: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/5.jpg)
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.
![Page 6: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/6.jpg)
Retrosynthetic Analysis
Lab Ring expansion
D-A
![Page 7: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/7.jpg)
Forward Synthesis
DA
Reductiveamin
![Page 8: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/8.jpg)
aza -prins
Dibromo cyclo prop
Ringexpansion
![Page 9: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/9.jpg)
Treatment of 11 with diphenyl disulfide
Vinylogouspummer
![Page 10: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/10.jpg)
![Page 11: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/11.jpg)
Treatment of 11 with isoamyl nitrite
![Page 12: Concise Total Synthesis of (+)-Lyconadin A Research by: Tohru Fukuyama Presentation by: Carl Brothers.](https://reader036.fdocuments.in/reader036/viewer/2022070413/5697bf9e1a28abf838c94633/html5/thumbnails/12.jpg)
•8.1% overall yield by nitrosoalkene method.•11.6% overall yield by sulfide method.
Michael