Presented by Michael Elbaum

A Synthesis of (+)-FR182877, Featuring Tandem Transannular Diels-Alder Reactions

Inspired by a Postulated Biogenesis

David A. Vosburg, Christopher D. Vanderwal, and Erik J. Sorensen

Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037

Presented by Michael Elbaum

Dr. Erik J. Sorensen

• Born and raised in upstate NY• Received B.S. in chemistry for Syracuse

University• As a graduate student at UC San Diego,

coauthored Classics in Total Synthesis• In 1995 received his PhD under Dr. K. C.

Nicolaou• 1995-1997 was a NSF postdoc under Dr. Samuel

Danishefsky at The Memorial Sloan-Kettering Cancer Center NY

• In 2001 became Associate Professor at The Scripps Research Institute

• Currently at Princeton Univeristy

(+)-FR182877

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- Used in cancer therapy

- Member of secondary metabolites that bind and stabilize cellular microtubules

- Exhibits potency comparable to Taxol

- No Prior Synthesis

- 12 stereo centers

- Strained bridgehead alkene

Retrosynthesis: Biosynthetic Pathway

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Stille Coupling

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Stille Cross-Coupling

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Forward Synthesis

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Forward Synthesis

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Coupling C1 C19

Tandem Diels-Alder

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Tandem Diels-Alder

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Forward Synthesis

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Conclusion

• Biogenetic pathways for the synthesis of complex natural products can provide insight into the synthesis

• Synthesis of polyunsaturated macrocycle can undergo cyclization to form complex molecules

• Diastereoselectrivity is intrinsic to the Diels-Alder cyclization

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