0. Krische’s Total Synthesis of Cyanolide A
Presented by BriAnne Bentivegna
May 7, 2013
University of Delaware
Waldeck, A.R.; Kriche, M.J. Angew. Chem. Int. Ed. 2013, 52, 4470

1. Michael J. Krische
B.S.in Chemistry from University of California at Berkeley (1989)
Fulbright Fellow at Helsinki University (1990)
Ph.D. in Chemistry from Stanford University ( )
NIH Post-Doc at Université Louis Pasteur ( )
Individual Career at the University of Texas at Austin
Assistant Professor of Chemistry ( )
Professor of Chemistry (2004-Present)
Robert A. Welch Chair in Science (2007-Present)
Awards include ACS Cope Scholar Award, ACS Elias J. Corey Award, National Science Foundation Career Award, Camille Dreyfus Teacher-Scholar Award and many more.
175 publications to date
160 publications from his independent career

2. Cyanolide A
Isolated from the Papua New Guinea cyanobacterium Lyungbya bouillonii
Exhibits potent molluscicidal activity against Biomphalaria glabrata, a water snail
This water snail is a vector of the human parasitic disease schistosomiasis which ranks second behind malaria among human parasitic diseases
There are drugs that exist to treat those who are infected but reducing or eliminating the population of these infected water snails is more desirable
Hence, efforts to synthesize Cyanolide A have been put forth by many chemists as an alternate molluscididal agent
A total of 6 chemists excluding Krische have synthesized Cynaolide A ranging from 18 to 22 total steps

3. Retrosynthesis

4. Beginning Steps

5. Ending Steps
Cyanolide A!!!

6. 2nd Generation Synthesis
Cyanolide A!!!

7. Conclusion
Cyanolide A was synthesized in 7 linear/11 total steps and 6 linear/10 total steps
NO Protecting Groups, Chiral Auxiliaries or Premetalated Carbon Nucleophiles were used!!!
Questions?

8. Double Allylation Mechanism
Kim, I.S.; Han, S.B.; Kische, M.J. J. Am. Chem. Soc. 2009, 131, 2514

9. Oxa-Michael Cyclization Mechanism
Fuwa, H.; Noguchi, T.; Noto, K. Sasaki, M. Org. Biomol. Chem. 2012, 10, 8108