Rychnovsky’s Formal Synthesis of
Leucascandrolide A
Presented by BriAnne Bentivegna
March 19, 2013
University of Delaware
Kopecky, D.J.; Rychnovsky, S.D. J. Am. Chem. Soc. 2001, 123, 8420
Scott D. Rychnovsky
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1981 - B.A. from University of California at Berkeley
1986 - PH.D. from Columbia University
1987 - NIH Postdoctoral Fellow at Harvard University
1988 - Faculty member at the University of Minnesota
1995 - Professor of Chemistry at the University of California – Irvine
Numerous Awards including Arthur C. Cope Scholar Award, Pfizer Research
Award in Synthetic Organic Chemistry and National Science Foundation
Presidential Young Investigator Award.
Associate Editor for The Journal of Organic Chemistry
Research interests include synthesis of rimocidin, phorboxazole A, epicalyxin F,
and leucascandrolide A.
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Leucascandrolide A
• First isolated by Pietra and coworkers in 1996 from the calcareous
sponge Leucascandra caveolata along the east coast of New
Caledonia
• Displays potent cytotoxic activity in vitro on human P388
(Leukemia) cancer cells as well as antifungal activity
• Synthesized by several groups including the Rychnovsky, Leighton
and Kozmin groups
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Dambrosio, M.; Guerriero, A.; Debitus, C.; Pietra, F. Helvetica Chimica Acta. 1996, 79, 51
Retrosynthesis
Yamaguchi-type
Cyclization
Aldol - Prins
Coupling
Noyori
Hydrogenation
Noyori
Hydrogenation
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Synthesis of Aldo-Prins Precursor #1
Noyori Hydrogenation
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Synthesis of Aldo-Prins Precursor #2
Noyori Hydrogenation
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Aldol-Prins Coupling
Aldol - Prins Coupling
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Synthesis of Leucascandrolide A Macrolide
Leucascandrolide A
Macrolide
Yamaguchi-type Cyclization
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Final Steps via Leighton
Horner-Wadsworth-Emmons
Leucascandrolide A!!!
Hornberger, K. R.; Hamblett, C. L.; Leighton, J. L. J. Am. Chem. Soc. 2000, 122, 12894
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Conclusion
• Leucascandrolide A Macrolide synthesized in 23 steps
• Leucascandrolide A synthesized in 25 steps with the help of
Leighton
Questions?
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