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, North Torrey Pines Road, La Jolla, California 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 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 (+)-FR 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 3 Stille Coupling 4 Stille Cross-Coupling 5 Forward Synthesis 6 7 Coupling C1 C19 Tandem Diels-Alder 8 9 Forward Synthesis 10 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 11