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Total Synthesis of (+)-Discodermolide

Total Synthesis of (+)-Discodermolide. CHEM635 Kelsey Roberts Group B February 19, 2013. Patterson, I*; Florence, G. J.; Gerlach, K.; Scott, J. P. Agnew. Chem. Int. Ed. 2000 , 39, 377-380. Ian Paterson. Born in 1954 in Dundee, Scottland B.S. in Chemistry from U of Saint Andrews, 1976

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Total Synthesis of (+)-Discodermolide

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  1. Total Synthesis of (+)-Discodermolide CHEM635 Kelsey Roberts Group B February 19, 2013 Patterson, I*; Florence, G. J.; Gerlach, K.; Scott, J. P. Agnew. Chem. Int. Ed. 2000, 39, 377-380.

  2. Ian Paterson • Born in 1954 in Dundee, Scottland • B.S. in Chemistry from U of Saint Andrews, 1976 • PhD from Cambridge under Ian Flemming, 1979 • NATO post-doctoral fellow with Gilbert Stork at Columbia • Lectureship at University College London • 1983-present Cambridge University Professor of Organic Chemistry and Fellow of Jesus College • 237 Publications to date. • Research focuses on synthetic methods, synthesis and structure determination of biologically active materials

  3. History of (+) Discodermolide • First isolated in 1990 by Gunasekera in Florida from the Caribbean sponge Discodermia dissoluta. • 13 Stereogenic centers, tetrasubstituted δ-lactone, on di and one tri-substituted Z-alkene, a carbamate, and a terminal Z-diene • Acts as a antimitotic agent by stabilizing microtubules and promotes polymerization of tubulin • Inhibits growth of breast cancer cells in vitro, resistant ovarian and colon cancer cells. • Before Ian Paterson, 2 total synthesis of (+)-Discodermolide (Schreiber et al) and 3 of (-)-Discodermolide (Kobayashi, Myles, Johns) • Schreiber et al determined absolute stereochemistry

  4. Retrosynthesis

  5. Synthesis of 2

  6. Synthesis of 3

  7. Synthesis of 3 Continued

  8. Synthesis of 4

  9. Synthesis of 5

  10. Synthesis of 5 Continued

  11. Final Steps to (+)-Discodermolide

  12. Conclusion • (+) Discodermolide synthesized in overall 7.7% yield • 27 steps for longest linear sequence

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