Download - Corey Basch Synthesis Presentation 4/30/13
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Total Syntheses of (-)-Acutumine and (-)-Dechloroacutumine
King, S. M.; Calandra, N. A.; Herzon, S. B. Angew. Chem. Int. Ed. 2013, 52, 3642-3645.
Corey BaschSynthesis Presentation
4/30/13
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Seth Herzon
2002- B.S. Chemistry, Temple University.
2006- PhD Chemistry, Harvard University.
2008-2012- Assistant Professor of Chemistry, Yale University.
2012-Present- Associate Professor, Yale.
19 Publications (independent career)-Total synthesis of natural products-MOA and target identification of anticancer natural products-Methodology-Reagent development
Awards: -Packard Fellowship-Sloan Fellowship-Cottrell Scholar Award-NSF Career Award-Eli Lilly New Faculty Award
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(-)-Acutumine/Dechloroacutumine
(-)-Acutumine:
- Isolated from Sinomenium acutum.- Tetracyclic, spirocycle, 5 stereocenters.- Inhibits human T-cell proliferation.- Improves object/social recognition, memory in rat model.- Only one other total synthesis reported (Castle, 2009).
(-)-Dechloroacutumine:
- Isolated from Menispermum dauricum (Asian moonseed).- Direct metabolite of (-)-Acutumine.- No previously reported total synthesis.
Menispermum dauricum
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Retrosynthesis
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Formation of the Arylacetylide from D-Ribose
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Addition of the Arylacetylide to the Bicyclic Core
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Hydrostannylation and Hosomi-Sakurai Allylation
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Setting the Oxidation State of the Spirocyclopentenone Ring and a Final Reduction
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• Longest linear sequence: 23 steps
• (-)-Acutumine: 0.43 %
• (-)-Dechloroacutumine: 1.5 %
• First reported total synthesis of (-)-Dechloroacutumine
• Second reported total synthesis of (-)-Acutumine
Overview
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