1. Malcolm P. Huestis Supervisor: Keith Fagnou 1

2. Isolation and structure elucidation: Aoki, S.; Watanabe, Y.; Sanagawa, M.; Setiawan, A.; Kotoku, N.; Kobayashi, M. J. Am. Chem. Soc. 2006, 128, 3148-3149. Marine Sponge Corticium simplex (22 mg from 1.5 kg organism) -Selectively inhibits angiogenesis. -IC 50 = 1.8 nM 2 -Anti-angiogenetic substances inhibit the formation of new capillary blood vessels. -Cancer, diabetic eye disease, rheumatoid arthritis

3. Total Synthesis: Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243. Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313. Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866. Partial Syntheses (all from 2008): Danishefsky – Sloan-Kettering Institute and Columbia University Corey – Harvard University Yamashita and Hirama – Tohoku University Sarpong – University of California (Berkeley) Gung – Miami University Kobayashi – Osaka University Highlight: Nising, C. F.; Bräse, S. Angew. Chem. Int. Ed. 2008, 47, 9389-9391. 3

4. 4 1) May 14 th, 2008 - Phil Baran – Highly chemoselective semi-synthetic strategy 2) August 14 th, 2008 - K.C. Nicolaou and David Chen – From the Hajos- Parrish bicyclic ketone 3) November 19 th, 2008 - Matthew Shair’s key step - An efficient aza-prins cyclization Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243. Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313. Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

5. 5 1)Phil Baran – -Radical ring expansion reaction -Co(III)-catalyzed alkene hydration -Alcohol-directed dibromination reaction -Chemo- and stereoselective double bond reduction 2)K.C. Nicolaou and David Chen – -A single cascade reaction to fuse the entire oxabicycle -Mild aldehyde alkynylation -IBX deprotects dithiane-protected carbonyl -IBX-mediated enone synthesis 3)Matthew Shair’s key step – -Late-stage aza-prins cyclization Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243. Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313. Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

6. 6 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

7. 7

8. 8

9. 9

10. 10 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

11. 11 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

12. 12 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

13. 13 Isayama, S.; Mukaiyama, T. Chem. Lett. 1989, 1071-1074. Takahiro, T.; Kunikawa, S.; Masuyama, A.; Nojima, M. Org. Lett. 2002, 4, 3595-3598.

14. 14 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

15. 15 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

16. 16 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

17. 17 Čeković, Ž. Tetrahedron 2003, 59, 8073-8090

18. 18 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

19. 19 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

20. 20 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

21. 21 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

22. 22 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

23. 23 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

24. 24 Barton, D. H. R.; O’Brian, R. E.; Sternhell, S. J. Chem. Soc. 1962, 470-476. Han, X. J.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600-7605.

25. 25 Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243.

26. 26 Barton, D. H. R.; O’Brian, R. E.; Sternhell, S. J. Chem. Soc. 1962, 470-476. Han, X. J.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600-7605.

27. 27 Barton, D. H. R.; O’Brian, R. E.; Sternhell, S. J. Chem. Soc. 1962, 470-476.

28. 28 Barton, D. H. R.; O’Brian, R. E.; Sternhell, S. J. Chem. Soc. 1962, 470-476. Han, X. J.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600-7605.

29. 29 Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313.

30. 30 Isaacs, R. C. A.; Di Grandi, M. J.; Danishefsky, S. J. J. Org. Chem. 1993, 58, 3938-3941. Hajos, Z. G.; Parrish, D. R. Org. Synth. 1990, Coll. Vol. 7, 363-368; 1985, 63, 26-36. Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615-1621. Eder, U.; Sauer, G.; Wiechert, R. Angew. Chem. Int. Ed. Engl. 1971, 10, 496-497.

31. 31 Clemente, F. R.; Houk, K. N. Angew. Chem. Int. Ed. 2004, 43, 5766-5768. Zhu, H.; Clemente, F. R.; Houk, K. N.; Meyer, M. P. J. Am. Chem. Soc. 2009, 131, 1632-1633. Hajos, Z. G.; Parrish, D. R. Org. Synth. 1990, Coll. Vol. 7, 363-368; 1985, 63, 26-36. Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615-1621.

32. 32 VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 17, 1973-1976. McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24, 979-982. Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem. 1974, 39, 3318-3326.

33. 33 Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-7287. Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507. Ohira, S. Synth. Commun. 1989, 19, 561-564. Müller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J. Synlett 1996, 521-522.

34. 34 Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507.

35. 35 Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-7287. Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507. Ohira, S. Synth. Commun. 1989, 19, 561-564. Müller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J. Synlett 1996, 521-522.

36. 36 Roth, G. J.; Liepold, B.; Müller, S. G.; Bestmann, H. J. Synlett 2004, 59-62.

37. 37 Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313.

38. 38 Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 50, 4467-4470. Nicolaou; K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem. Soc. 2004, 126, 5192-5201.

39. 39 Nicolaou; K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem. Soc. 2004, 126, 5192-5201.

40. 40 Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 50, 4467-4470. Nicolaou; K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem. Soc. 2004, 126, 5192-5201.

41. 41 Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313. Same product was independently isolated: Yamashita, S.; Iso, K.; Hirama, M. Org. Lett. 2008, 10, 3413-3415.

42. 42 Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 1357-1358. Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507. McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24, 979-982.

43. 43 Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 1357-1358.

44. 44 Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 1357-1358. Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505-5507. McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24, 979-982.

45. 45 Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed. 2002, 41, 996-1000. Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226-2227.

46. 46 Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem. Soc. 2000, 122, 7596-7597. Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y.-L. J. Am. Chem. Soc. 2002, 124, 2245-2258. Nicolaou, K. C.; Montagnon, T.; Baran, P. S. Angew. Chem. Int. Ed. 2002, 41, 993-996. Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed. 2002, 41, 996-1000.

47. 47 Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed. 2002, 41, 996-1000. Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226-2227.

48. 48 Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed. 2002, 41, 996-1000. Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226-2227.

49. 49 Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew. Chem. Int. Ed. 2002, 41, 996-1000. Luche, J.-L. J. Am. Chem. Soc. 1978, 100, 2226-2227.

50. 50 Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

51. 51 Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

52. 52 Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

53. 53 Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

54. 54 1) May 14 th, 2008 - Phil Baran 2) August 14 th, 2008 - K.C. Nicolaou and David Chen 3) November 19 th, 2008 - Matthew Shair Shenvi, R. A.; Guerrero, C. A.; Shi, J.; Li, C.-C.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7241-7243. Nicolaou, K. C.; Sun, Y.-P.; Peng, X.-S.; Polet, D.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 7310-7313. Lee, H. M.; Nieto-Oberhuber, C.; Shair, M. D. J. Am. Chem. Soc. 2008, 130, 16864-16866.

55. Front: Ho-Yan SUN Dave STUART Malcolm HUESTIS Mégan BERTRAND-LAPERLE (gone) David LAPOINTE Sophie ROUSSEAUX Olivier RENÉ Chris WHIPP Back: Ivan PETROV Benoît LIÉGAULT Elisia VILLEMURE (gone) Daniel SHORE Derek SCHIPPER Nicolas GUIMOND Pamela AL-SABEH Prof. Keith Fagnou Not shown: Michelle KUHN Kevin BURGESS