1. Synthesis of Leucascandrolide A via a Spontaneous Macrolactolization J. Am. Chem. Soc. 2002, 124, 13670-13671 Presented by Vijayarajan Devannah 3/19/2013 Ying Wang, Jelena Janjic, Sergey A. Kozmin

2. About Professor Sergey A. Kozmin Education and Professional 1991-1993 Undergraduate Research Assistant with Professor Irina P. Beletskaya Lomonosov Moscow State University, Moscow, Russia 1993-1998 Graduate Research Assistant with Professor Viresh H. RawalUniversity of Chicago, Chicago, Illinois 1998-2000 Postdoctoral Associate with Professor Amos B. Smith, III University of Pennsylvania, Philadelphia, Pennsylvania 2000-2006 Assistant Professor, University of Chicago 2006-2011 Associate Professor, University of Chicago 2011-present Professor, University of Chicago Notable Awards 2003 Alfred P. Sloan Fellow 2004 American Cancer Society Research Scholar 2004 Amgen Young Investigator’s Award 2004 Camille Dreyfus Teacher-Scholar Award 2005 NSF CAREER Award 2005 GlaxoSmithKline Chemistry Research Scholar 1

3. About Leucascandrolide A Its is a highly bioactive marine macrolide isolated from new genus of calcerous sponges Leucascandra caveolata. It displays potent cytotoxicity against KB and P388 tumor cell lines ( IC 50 50 ng/ml and 0.25 μg/mL respectively), and it also a strong inhibitor of animal-pathogenic yeast candida albicans. Structural Features of Leucascandrolide A It possess a 14 membered lactone It includes dioxotricyclic core It is highly unsaturated and contains oxazole in its side chain. 2

4. Retrosynthesis 3

5. Synthesis of C 1 -C 15 Fragment 4 Scheme 2 Scheme 3

6. Continues…… 5 Scheme 4 Scheme 5

7. Formation of crucial Macrocycle 6 Scheme 5

8. Synthesis of Oxazole side chain and completion of the target Leucascandrolide A 7 Scheme 6

9. Conclusion Racemic Leucascandrolide A was synthesized in longest linear sequence of 18 steps from commercially available precursors. 500 MHz 1 H NMR and 125 MHz 13 C NMR spectra of synthetic Leucascandrolide A was in excellent agreement with those reported in literature. Total yield is 2% 8

10. Thank You 9