Université de Montréal "You eat, drink, and sleep your molecule" (Phil S. Baran) Guillaume Barbe Charette’s Laboratories Université de Montréal October 30th 2006

Phil S. Baran Date/Place of Birth: 10 Aug 1977 / Denville, NJ, USA Education 1991 - 1995 Simultaneous high school graduation from Mt. Dora High School and A.A. degree with honors from Lake Sumter Community College, Florida 1995 - 1997 B.S. with Honors in Chemistry, New York University Advisor: Professor D.I. Schuster 1997 - 2001 Ph.D. graduate student in Chemistry, The Scripps Research Institute Advisor: Professor K.C. Nicolaou 2001 - 2003 Postdoctoral Associate, Harvard University Advisor: Professor E.J. Corey Career July, 2006 Associate Professor of Chemistry (with Tenure) June, 2003 Assistant Professor of Chemistry

Phil S. Baran: Awards Pre to PostDoctoral • Nobel Laureate Signature Award in Chemistry, ACS, 2003 • National Institutes of Health Post-Doctoral Fellowship Award, Harvard, 2001-2003 • Hoffmann-La Roche Award for Excellence in Organic Chemistry, 2000 • Lesly Starr Shelton Award for Excellence in Chemistry Graduate Studies, 2000 • National Science Foundation Pre-Doctoral Fellowship Award, Scripps, 1998–2001 • William and Sharon Bauce Family Foundation Fellowship Award, Scripps, 1997 • Dean’s Undergraduate Research Fund Award in Chemistry, NYU, 1996-1997 • George Granger Brown Award for Excellence in Chemistry, NYU, 1996-1997 • NYU College of Art and Sciences Scholarship, 1995-1997 • Herman and Margaret Sokol Chemistry Fellowship, NYU, 1995-1997

Phil S. Baran: Awards Pre and PostDoctoral Nobel Laureate Signature Award in Chemistry Purpose: To recognize an outstanding graduate student and her or his preceptor(s), in the field of chemistry, as broadly defined. "Phil Baran was a phenomenal student. Tenacious, enthusiastic, brilliant, and imaginative. I think he is now a formidable synthetic chemist with an exciting career ahead of him." (Nicolaou) "Phil has a towering intellect and is a young person of great originality and motivation. I feel certain that he is destined to be one of the superstars of organic chemistry for years to come." (Corey) C&EN : January 6, 2003, Volume 81, Number 01, pp. 38-43

Phil S. Baran: Awards Independent career • National Fresenius Award, 2007 • Pfizer Award for Creativity in Organic Synthesis, 2006 • Beckman Foundation Fellow, 2006 – 2008 • Alfred P. Sloan Foundation Fellow, 2006 – 2008 • BMS Unrestricted “Freedom to Discover” Grant, 2006 – 2010 • NSF CAREER award, 2006 – 2010 • Eli Lilly Young Investigator Award, 2005-2006 • AstraZeneca Excellence in Chemistry Award, 2005 • DuPont Young Professor Award, 2005 • Roche Excellence in Chemistry Award, 2005 • Amgen Young Investigator Award, 2005 • Searle Scholar Award, 2005 • GlaxoSmithKline Chemistry Scholar Award, 2005-2006

Baran’s Publications: Schuster Fullerene Chemistry 27. MacMahon, S.; Fong, R.; Baran, P.S.; Safonov, I.; Wilson, S.R.; Schuster, D.I. J. Org. Chem. 2001, 66; 5449-5455. 24. Wilson, S.R.; Baran, Phil S.; Schuster, D.I.; Goh, S.K.; Marynick, D.S. manuscript in preparation. 14. Baran, P.S.; Khan, A.U.; Schuster, D.I. Sci. Tech. 1999, 7, 921-925. 4. Schuster, D.I.; Baran, P.S.; Hatch, R.K.; Khan, A.U.; Wilson, S.R. Chem. Commun. 1998, 22, 2493-2494. 3. Safonov, I.G.; Baran, P.S.; Schuster, D.I. Tetrahedron Lett. 1997, 38, 8133-8136. 2. Baran, P.S.; Monaco, R.R.; Khan, A.U.; Schuster, D.I.; Wilson, S.R. J. Am. Chem. Soc. 1997, 119, 8363-8364. 1. Baran, P.S.; Monaco, R.R.; Khan, A.U.; Schuster, D.I.; Soulas, P.; Echegoyen, L. Proc. - Electrochem. Soc. 1997, 97-14 (Recent Advances in the Chemistry and Physics of Fullerenes and Related Materials), 25-36.

Baran’s Publications: Nicolaou 39. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720. 35. Nicolaou, K.C.; Jung, J.; Yoon, W. H.; Fong, K. C.; Choi, H.; He, Y.; Zhong, Y. L.; Baran, P. S. J. Am. Chem. Soc. 2002, 124, 2183 - 2189. 34. Nicolaou, K.C.; Baran, P. S., Zhong, Y. L.; Fong, K. C.; Choi, H. J. Am. Chem. Soc. 2002, 124, 2190 - 2201. 33. Nicolaou, K.C.; Zhong, Y. L.; Baran, P. S.; Jung, J.; Choi, H.; Yoon, W. H. J. Am. Chem. Soc. 2002, 124, 2202 - 2211. 17. Nicolaou, K.C.; Jung, J.-K.; Yoon, W.-Y.; He, Y.; Zhong, Y.-L.; Baran, P.S. Angew. Chem. Int. Ed. 2000, 39, 1829-1832. 8. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675. 7. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Fong, K.C.; He, Y.; Yoon, W.H.; Choi, H.S. Angew. Chem. Int. Ed. 1999, 38, 1676-1678. 6. Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66. 5. Nicolaou, K.C.; Baran, P.S.; Jautelat, R.; He, Y.; Fong, K.C.; Choi, H.-S.; Yoon, W.H.; Zhong, Y.-L. A Angew. Chem. Int. Ed. 1999, 38, 549-552.

Baran’s Publications: Nicolaou Iodine(V) Reactions 37. Nicolaou, K.C.; Montagnon, T.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 1386-1389. 36. Nicolaou, K.C.; Montagnon, T.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 993 - 996. 32. Nicolaou, K.C.; Baran, P. S.; Zhong, Y. L.; Sugita, K. J. Am. Chem. Soc. 2002, 124, 2212 - 2220. 31. Nicolaou, K.C.; Sugita, K.; Baran, P. S.; Zhong, Y. L. J. Am. Chem. Soc. 2002, 124, 2221 - 2232. 30. Nicolaou, K.C.; Baran, P. S.; Zhong, Y. L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233 - 2244. 29. Nicolaou, K.C.; Montagnon, T.; Baran, P. S.; Zhong, Y. L. J. Am. Chem. Soc. 2002, 124, 2245 - 2258. 26. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.L. J. Am. Chem. Soc. 2001, 123, 3183 - 3185. 25. Nicolaou, K.C.; Zhong, Y. L.; Baran, P.S.; Sugita, K. Angew. Chem. Int. Ed. 2001, 40, 2145. 23. Nicolaou, K.C.; Sugita, K.; Baran, P.S; Zhong, Y.-L. Angew. Chem. Int. Ed. 2001, 40, 207-210. 22. Nicolaou, K.C.; Baran, P.S.; Kranich, R.; Zhong, Y.L.; Sugita, K.; Zou, N. Angew. Chem. Int. Ed. 2001, 40, 202-206. 19. Nicolaou, K.C.; Zhong, Y.-L.; Baran, Phil S. J. Am. Chem. Soc. 2000, 122, 7596-7597. 18. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Vega, J.A. Angew. Chem. Int. Ed. 2000, 39, 2525-2529. 13. Nicolaou, K.C.; Zhong, Y.-L.; Baran, P.S. Angew. Chem. Int. Ed. 2000, 39, 622-625. 12. Nicolaou, K.C.; Zhong, Y.-L.; Baran, P.S. Angew. Chem. Int. Ed. 2000, 39, 625-628.

Baran’s Publications: Nicolaou Synthesis of Hindered a-Diazoketones via Acyl Mesylates 9. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Fong, K.C.; He, Y.; Yoon, W.H. Org. Lett. 1999, 1, 883-886. a-Sulfonated Ketones 28. Nicolaou, K.C.; Montagnon, T.; Ulven, T.; Baran, P. S.; Zhong, Y. L.; Sarabia, F. J. Am. Chem. Soc. 2002, 124, 5718 - 5728. 20. Nicolaou, K.C.; Baran, P.S.; Zhong, Y.L. J. Am. Chem. Soc. 2000, 122, 10246-10248. Mild and Selective Homologation of Hindered Aldehydes in the Presence of Ketones 16. Nicolaou, K.C.; Vassilikogiannakis, G.; Kranich, R.; Baran, P.S.; Zhong, Y.L.; Natarajan, S. Org. Lett. 2000, 2, 1895-1898. The Art and Science of Total Synthesis at the Dawn of the Twenty-first Century 21. Nicolaou, K.C.; Vourloumis, D.; Winssinger, N.; Baran, P.S. Angew. Chem. Int. Ed. 2000, 39, 44-122.

Baran’s Publications: Nicolaou 15. Nicolaou, K.C.; Vassilikogiannakis, G.; Simonsen, K.B.; Baran, P.S.; Zhong, Y.-L.; Vidali, V.P.; Pitsinos, E.N.; Couladouros, E.A. J. Am. Chem. Soc. 2000, 122, 3071 - 3079. 11. Nicolaou, K.C.; Jautelat, R.; Vassilikogiannakis, G.; Baran, P.S.; Simonsen, K. Chem. Eur. J. 1999, 5, 3651-3665. 10. Nicolaou, K.C.; Simonsen, K.S.; Vassilikogiannakis, G.; Baran, P.S.; Vidali, V.P.; Pitsinos, E.N.; Couladouros, E.A. Angew. Chem. Int. Ed. 1999, 38, 3555-3559.

Baran’s Publications: Corey 38. Baran, P. S.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 7904 - 7905. 40. Baran, P. S.; Guerrero, C. A.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 5628 - 5629. 41. Baran, P. S.; Guerrero, C. A.; Corey, E. J. Org. Lett. 2003, 5, 1999 - 2001.

Baran’s Publications 53. Baran, P.S.; Hafensteiner, B.D.; Ambhaikar, N. B.; Guerrero, C. A.; Gallagher, J. D. Enantioselective Total Synthesis of Avrainvillamide and the Stephacidins. J. Am. Chem. Soc. 2006, 128, 8678-8693. 48. Baran, P. S.; Guerrero, C.A.; Hafensteiner, B.D.; Ambhaikar, N.B. Total synthesis of Avrainvillamide (CJ-17,665) and Stephacidin B, Angew. Chem. Int. Ed. 2005, 44, 3892-3895. 46. Baran, P. S.; Guerrero, C.A.; Ambhaikar, N.B.; Hafensteiner, B.D. Short, Enantioselective Total Synthesis of Stephacidin A, Angew. Chem. Int. Ed. 2005, 44, 606-609.

Baran’s Publications 52. Northrop, B.H.; O'Malley, D.P.; Zografos A. L.; Baran, P.S.; Houk, K. N. Mechanism of the Vinylcyclobutane Rearrangement of Sceptrin to Ageliferin and Nagelamide E. Angew. Chem. Int. Ed. 2006, 45, 4126 –4130. 50. Baran, P. S.; Li, K; O'Malley, D.P.; Mitsos, C. Short, Enantioselective Total Synthesis of Sceptrin and Ageliferin by Programmed Oxaquadricyclane Fragmentation. Angew. Chem. Int. Ed. 2006, 45, 249 –252. 43. Baran, P.S.; O'Malley, D.P.; Zografos, A.L. Sceptrin as a Potential Biosynthetic Precursor to Complex Pyrrole-Imidazole Alkaloids: The Total Synthesis of Ageliferin, Angew. Chem. Int. Ed. 2004, 43, 2674-2677.  42. Baran, P.S.; Zografos, A.L.; O'Malley, D.P. Short Total Synthesis of Sceptrin, J. Am. Chem. Soc. 2004, 126, 3726-3727.

Baran’s Publications 55. Baran, P. S.; Shenvi, R. A. Total Synthesis of (±)–Chartelline C, J. Am. Chem. Soc. 2006, 128, in press. 47. Baran, P. S.; Shenvi, R.A.; Mitsos, C.A. A Remarkable Ring Contraction En Route to the Chartelline Alkaloids, Angew. Chem. Int. Ed. 2005, 44, 3714-3717. 51. Baran, P. S.; Burns, N. Z. Total Synthesis of (±)-Haouamine A. J. Am. Chem. Soc.; 2006; 128; 3908 - 3909.

Baran’s Publications 54. Baran, P. S.; DeMartino, M. P. Intermolecular Enolate Heterocoupling, Angew. Chem. Int. Ed. 2006, 45, in press. 49. Baran, P. S.; Richter, J. M. Enantioselective Total Syntheses of Welwitindolinone A and Fischerindoles I and G, J. Am. Chem. Soc.; 2005; 127(44); 15394-15396. 45. Baran, P.S.; Richter, J.M.; Lin, D.W. Direct Coupling of Pyrroles with Carbonyl Compounds: Short, Enantioselective Synthesis of (S)-Ketorolac, Angew. Chem. Int. Ed. 2005, 44, 609-612. 44. Baran, P.S.; Richter, J.M. Direct Coupling of Indoles with Carbonyl Compounds: Short, Enantioselective, Gram-Scale Synthetic Entry into the Hapalindole and Fischerindole Alkaloid Families, J. Am. Chem. Soc. 2004, 126, 7450-7451.

CP Molecules “New natural products have unusual structures” “Fermentation broths of a still-unidentified fungus have yielded two compounds that are promising leads to drugs for lowering serum cholesterol and treating cancer. In addition to their medicinal promise, the two compounds have unusual structures that make them attractive synthetic targets.” “Both compounds inhibit the enzymes squalene synthase and farnesyl protein transferase. Squalene synthase catalyzes condensation of two molecules of the C15 sesquiterpenoid farnesyl pyrophosphate to squalene, with presqualene pyrophosphate as a step on the way. This reaction is one in the overall biosynthesis of cholesterol. The hope is that such compounds will lead to new cholesterol-lowering drugs. Farnesyl protein 1 transferase mediates farnesylation of the protein p21, which is the product of the ras oncogene. A one-amino acid mutation of p21 renders it permanently activated, so that it pushes regulation of cell growth and division out of control. Here, the hope is that the Pfizer compounds will inhibit a step that may be essential to p21 activity and thus to the carcinogenic process.” Stinson, S. Chem. Eng. News 1995, 73, 29.

CP Molecules: Setting the floor to Baran [3,3]-sigmatropic rearrangement approach Nicolaou, K. C.; Postema, M. H. D.; Yang, G. Angew. Chem. Int. Ed. 1997, 36, 2821-2823.

CP Molecules: Setting the floor to Baran [3,3]-sigmatropic rearrangement approach Nicolaou, K. C.; Postema, M. H. D.; Yang, G. Angew. Chem. Int. Ed. 1997, 36, 2821-2823.

CP Molecules: Setting the floor to Baran Diels-Alder approach Nicolaou, K. C.; Härter, M. W.; Boulton, L.; Jandeleit, B. Angew. Chem. Int. Ed. 1997, 36, 1194-1196.

CP Molecules: Setting the floor to Baran Diels-Alder approach Nicolaou, K. C.; Härter, M. W.; Boulton, L.; Jandeleit, B. Angew. Chem. Int. Ed. 1997, 36, 1194-1196.

CP Molecules: Diels-Alder Scale Up Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675.

CP Molecules: The Maleic Anhydride Hurdle While improving and scaling up the Diels-Alder sequence (hundreds of grams), many approach to the anhydride met with failure. Mid-September 1997, the CP-team halted the studies on the anhydride formation to conclude the scale up. Beginning of December, 1997, the studies directed toward the maleic anhydride problem resumed. « Shortly before New Year’s eve, 1997, a rather daring strategy towards the anhydride moiety was conceived… » Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Maleic Anhydride Strategy Nicolaou, K.C.; Baran, P.S.; Jautelat, R.; He, Y.; Fong, K.C.; Choi, H.-S.; Yoon, W.H.; Zhong, Y.-L. A Angew. Chem. Int. Ed. 1999, 38, 549-552.

CP Molecules: Maleic Anhydride Synthesis “With the a,b-unsaturated ester in hand, we proceeded at a furious pace which reached a climax at 2:00 a.m. on January 1, 1998, wherein we had synthesized the cyanodiol…” “One of us (K.C.N.) will never forget the scene in the laboratory on that day in January 1998, who upon arrival at 8:00 a.m. found the other (P.S.B.) fast asleep on his desk with a clean NMR spectrum of compound [] by his side.” Nicolaou, K.C.; Baran, P.S.; Jautelat, R.; He, Y.; Fong, K.C.; Choi, H.-S.; Yoon, W.H.; Zhong, Y.-L. A Angew. Chem. Int. Ed. 1999, 38, 549-552. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Maleic Anhydride Synthesis “It would take another seven weeks before we finally found reliable conditions for the conversion of cyanodiol [] into maleic anhydride []…” Nicolaou, K.C.; Baran, P.S.; Jautelat, R.; He, Y.; Fong, K.C.; Choi, H.-S.; Yoon, W.H.; Zhong, Y.-L. A Angew. Chem. Int. Ed. 1999, 38, 549-552. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Maleic Anhydride Synthesis Nicolaou, K.C.; Baran, P.S.; Jautelat, R.; He, Y.; Fong, K.C.; Choi, H.-S.; Yoon, W.H.; Zhong, Y.-L. A Angew. Chem. Int. Ed. 1999, 38, 549-552.

CP Molecules: Maleic Anhydride Synthesis “Despite the extraordinary chemistry involved in this cascade in which maleic anhydride is formed, we restrained ourselves from submitting a paper describing the results until later on in 1998 when further progress toward the CP molecules was made.” Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: g-Hydroxylactone Hurdle “One of us took a trip downstairs to discuss this problem with Professor Erik Sorensen, he drew our attention to a paper of D. P. Curran…” Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: g-Hydroxylactone Hurdle “One of us took a trip downstairs to discuss this problem with Professor Erik Sorensen, he drew our attention to a paper of D. P. Curran…” Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: g-Hydroxylactone Hurdle Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66.

CP Molecules: g-Hydroxylactone Hurdle Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66.

CP Molecules: g-Hydroxylactone Hurdle Nicolaou, K.C.; He, Y.; Fong, K.C.; Yoon, W.H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P.S. Org. Lett. 1999, 1, 63-66.

CP Molecules: Real Model Synthesis Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675.

CP Molecules: Real Model Synthesis “In the midst of their desperation and hope, Yong-Li Zhong and Phil […] proceeded to design, in complete secrecy (from K.C.N.), an experiment […] in refluxing benzene with excess DMP! […] had they informed me […], I would have most likely instructed them […]against this course of action in light of the assumption that DMP could possibly be explosive at high temperatures. Their plot was, therefore, perfect…” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Homologation “My (K.C.N.) first reaction was to attribute this failure to the “inadequate” experimental skills of my co-workers; after all, I said, “This is a textbook example of the easiest transformations in organic chemistry!” However, despite repeated attempts, […] we were consistently unsuccessful. I was wrong and I apologized profusely to my very capable co-workers!” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Homologation “In the midst of this chaos when everyone was following their own intuition, I (K.C.N.) approached Phil and asked what strategy he was following. “I have an idea,” he said. “It’s simple.” What he had in mind was the use of an amide as a protecting group for the carboxylic acid…” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: DMP Surprise “…it did not help us at the time and we decided to put this strange discovery on the shelf (but not under the carpet!) until after the total synthesis was complete.” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Choi, H.-S.; Yoon, W.H.; He, Y.; Fong, K.C. Angew. Chem. Int. Ed. 1999, 38, 1669-1675. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Testing Baran! “Early one morning, after another failure, I (K.C.N.) called Phil to my office, sat him down and said, “This project is always in shambles, and it is very painful to everyone. I think we should cut our losses and just forget about the CP molecules. I would not think any less of you if you stop now.” “Phil’s eyes widened and he immediately declared, “Impossible, I will never stop until CP has fallen and I know Zhong feels the same way. This is what a PhD is all about, isn’t it?” “OK, good, you passed the test. Now you can go back to work...”” Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Final Route “During this period, I (K.C.N.) would often find Zhong and Phil either fast asleep in the mornings or working in eight-hour shifts exchanging material back and forth. As one rested, the other worked; my contribution was to bring them occasional sustenance in the form of sandwiches in the lab!” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Fong, K.C.; He, Y.; Yoon, W.H.; Choi, H.S. Angew. Chem. Int. Ed. 1999, 38, 1676-1678. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

CP Molecules: Final Route “The final reaction was set up at 1:00 a.m. on April 12, 1999. A few hours later it was done […]! I (K.C.N.) was to learn of the athlos upon my arrival in the lab at 8:00 a.m. that day. Needless to say, pure adrenaline kept Phil and Zhong awake past the successful isolation of CP-225,917( 2) and its subsequent conversion into CP-263,114 (1). Within 24 hours of that final blow, two communications were dispatched to Angewandte Chemie.” Nicolaou, K.C.; Baran, P.S.; Zhong, Y.-L.; Fong, K.C.; He, Y.; Yoon, W.H.; Choi, H.S. Angew. Chem. Int. Ed. 1999, 38, 1676-1678. Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

Triumphant CP-Team Nicolaou, K.C.; Baran, P.S. Angew. Chem. Int. Ed. 2002, 41, 2678 - 2720.

Total Synthesis of Haouamine A 51. Baran, P. S.; Burns, N. Z. Total Synthesis of (±)-Haouamine A. J. Am. Chem. Soc.; 2006; 128; 3908 - 3909.

Total Synthesis of Haouamine A Baran, P. S.; Burns, N. Z. J. Am. Chem. Soc. 2006, 128, 3908 - 3909.

Total Synthesis of Haouamine A Baran, P. S.; Burns, N. Z. J. Am. Chem. Soc. 2006, 128, 3908 - 3909.

Total Synthesis of Chartelline 55. Baran, P. S.; Shenvi, R. A. Total Synthesis of (±)–Chartelline C, J. Am. Chem. Soc. 2006, 128, in press. 47. Baran, P. S.; Shenvi, R.A.; Mitsos, C.A. A Remarkable Ring Contraction En Route to the Chartelline Alkaloids, Angew. Chem. Int. Ed. 2005, 44, 3714-3717.

Total Synthesis of Chartelline Baran, P. S.; Shenvi, R.A.; Mitsos, C.A. Angew. Chem. Int. Ed. 2005, 44, 3714-3717.

Total Synthesis of Chartelline Baran, P. S.; Shenvi, R.A.; Mitsos, C.A. Angew. Chem. Int. Ed. 2005, 44, 3714-3717.

Total Synthesis of Chartelline Baran, P. S.; Shenvi, R. A. J. Am. Chem. Soc. 2006, 128, in press.

Total Synthesis of Sceptrin 52. Northrop, B.H.; O'Malley, D.P.; Zografos A. L.; Baran, P.S.; Houk, K. N. Mechanism of the Vinylcyclobutane Rearrangement of Sceptrin to Ageliferin and Nagelamide E. Angew. Chem. Int. Ed. 2006, 45, 4126 –4130. 50. Baran, P. S.; Li, K; O'Malley, D.P.; Mitsos, C. Short, Enantioselective Total Synthesis of Sceptrin and Ageliferin by Programmed Oxaquadricyclane Fragmentation. Angew. Chem. Int. Ed. 2006, 45, 249 –252. 43. Baran, P.S.; O'Malley, D.P.; Zografos, A.L. Sceptrin as a Potential Biosynthetic Precursor to Complex Pyrrole-Imidazole Alkaloids: The Total Synthesis of Ageliferin, Angew. Chem. Int. Ed. 2004, 43, 2674-2677.  42. Baran, P.S.; Zografos, A.L.; O'Malley, D.P. Short Total Synthesis of Sceptrin, J. Am. Chem. Soc. 2004, 126, 3726-3727.

Total Synthesis of rac-Sceptrin Baran, P. S.; Zografos, A. L.; O'Malley, D. P. J. Am. Chem. Soc. 2004, 126, 3726-3727.

Total Synthesis of (+)-Sceptrin Baran, P. S.; Li, K.; O'Malley, D. P.; Mitsos, C. Angew. Chem. Int. Ed. 2006, 45, 249 –252.

Total Synthesis of (+)-Sceptrin Baran, P. S.; Li, K.; O'Malley, D. P.; Mitsos, C. Angew. Chem. Int. Ed. 2006, 45, 249 –252.

(-)-Ageliferin and Nagelamide E Baran, P. S.; O'Malley, D. P.; Zografos, A. L. Angew. Chem. Int. Ed. 2004, 43, 2674-2677. Northrop, B. H.; O'Malley, D. P.; Zografos A. L.; Baran, P. S.; Houk, K. N. Angew. Chem. Int. Ed. 2006, 45, 4126 –4130.

(-)-Ageliferin and Nagelamide E Baran, P. S.; O'Malley, D. P.; Zografos, A. L. Angew. Chem. Int. Ed. 2004, 43, 2674-2677. Northrop, B. H.; O'Malley, D. P.; Zografos A. L.; Baran, P. S.; Houk, K. N. Angew. Chem. Int. Ed. 2006, 45, 4126 –4130.

(-)-Ageliferin and Nagelamide E Baran, P. S.; O'Malley, D. P.; Zografos, A. L. Angew. Chem. Int. Ed. 2004, 43, 2674-2677. Northrop, B. H.; O'Malley, D. P.; Zografos A. L.; Baran, P. S.; Houk, K. N. Angew. Chem. Int. Ed. 2006, 45, 4126 –4130.

Baran’s Methodology 54. Baran, P. S.; DeMartino, M. P. Intermolecular Enolate Heterocoupling, Angew. Chem. Int. Ed. 2006, 45, in press. 49. Baran, P. S.; Richter, J. M. Enantioselective Total Syntheses of Welwitindolinone A and Fischerindoles I and G, J. Am. Chem. Soc.; 2005; 127(44); 15394-15396. 45. Baran, P.S.; Richter, J.M.; Lin, D.W. Direct Coupling of Pyrroles with Carbonyl Compounds: Short, Enantioselective Synthesis of (S)-Ketorolac, Angew. Chem. Int. Ed. 2005, 44, 609-612. 44. Baran, P.S.; Richter, J.M. Direct Coupling of Indoles with Carbonyl Compounds: Short, Enantioselective, Gram-Scale Synthetic Entry into the Hapalindole and Fischerindole Alkaloid Families, J. Am. Chem. Soc. 2004, 126, 7450-7451.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126, 7450-7451.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126, 7450-7451.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126, 7450-7451.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126, 7450-7451.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2005; 127, 15394-15396.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2005; 127, 15394-15396.

Baran’s Methodology Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2005; 127, 15394-15396.

Baran’s Methodology Baran, P. S.; Richter, J. M.; Lin, D. W. Angew. Chem. Int. Ed. 2005, 44, 609-612.

Baran’s Methodology Baran, P. S.; Richter, J. M.; Lin, D. W. Angew. Chem. Int. Ed. 2005, 44, 609-612.

Baran’s Methodology Baran, P. S.; DeMartino, M. P. Angew. Chem. Int. Ed. 2006, 45, in press.

Baran’s Methodology Baran, P. S.; DeMartino, M. P. Angew. Chem. Int. Ed. 2006, 45, in press.

Baran’s Methodology Baran, P. S.; DeMartino, M. P. Angew. Chem. Int. Ed. 2006, 45, in press.

Race for Molecular Summits Robert F. Service Science 9 July 1999 : Vol Race for Molecular Summits Robert F. Service Science 9 July 1999 : Vol. 285. no. 5425, pp. 184 - 187 In a branch of chemistry called TOTAL SYNTHESIS, glory goes to the first team to reproduce a complex molecule from simple ingredients. But some wonder whether the competition is healthy. “It used to be that the way to learn the principles was to engage in the second exercise,” says [Nicolaou]. “That is less and less true. There's the rub.” “That much I'm ready to concede,” says Danishefsky. The chemistry that is developed on the climb up the mountain “doesn't impact as many other projects” as the discoveries made in previous decades, he says. “I'm sure that's true,” agrees Scripps total synthesis chemist Dale Boger. “At some point, [the chemistry] becomes so well developed that it becomes harder to justify chemistry for chemistry's sake.” “The quickest way to make a molecule is not to discover new reactions, but to use known reactions,” says Jacobsen. “Rarely do you see a lot of new chemistry come out of that effort.”

Final quote… Small Molecule Natural Products in the Discovery of Therapeutic Agents: The Synthesis Connection The main case for SMNPs as a means of discovering valuable leads is that such structures often allow for entry into the discovery progression at a much more advanced stage than does the screening of standard diversity libraries which lack comparable pedigree or intellectual coherence. Wilson, R. M.; Danishefsky, S. J. J. Org. Chem. 2006, 71, 8329-8351.