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Enantioselective Total Synthesis of Kibdelone C

Enantioselective Total Synthesis of Kibdelone C. A presentation by Guillaume Pelletier November 2 th 2011. Porco, J. A., Jr. JACS 2011 , 133 , 9952. Porco, J. A., Jr. ACIE 2011 , 50 , 2511. Reddy, J. M. JACS , 2011 , 133 , 9956. Capon, R. J. OL 2006 , 8 , 5267.

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Enantioselective Total Synthesis of Kibdelone C

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  1. Enantioselective Total Synthesis of Kibdelone C A presentation by Guillaume Pelletier November 2th 2011 Porco, J. A., Jr. JACS2011, 133, 9952. Porco, J. A., Jr. ACIE 2011, 50, 2511. Reddy, J. M. JACS, 2011, 133, 9956. Capon, R. J. OL 2006, 8, 5267.

  2. Kibdelone C and Congeners Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Ratnayake, R.; Lacey, E.; Tennant, S.; Gill, J. H.; Capon, R. J. Chem. Eur. J. 2007, 13, 1610-11619.

  3. Kibdelone C Retrosynthetic Analysis Evaluation kibdelone C in the NCI 60-cell panel of human cancer cell lines revealed that they are active at low nanomolar concentrations against a number of human tumor cell lines : GI50 of 1.2 nm against a SR (leukemia) tumor cell line GI50 of <1 nm against SN12C (renal) cell carcinoma Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  4. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Nicolaou, K. C.; Lim, H.-Y.; Becker, J.; Lemire, A.; Neubauer, T.; Montero, A. J. Am. Chem. Soc. 2009, 131, 14812.

  5. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Guyot, M.; Molho, D. Tetrahedron Lett. 1973, 73, 3433-3436.

  6. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Guyot, M.; Molho, D. Tetrahedron Lett. 1973, 73, 3433-3436.

  7. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  8. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  9. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  10. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Carey, F. A. in Organic Chemistry, McGraw-Hill Science Edition, 4th edition, Ch. 24.

  11. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  12. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Wymann, W. E.; Davis, R.; Patterson, J. W.; Pfister, J. R.Synth. Commun. 1988, 18, 1379-1384.

  13. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Lafranchi, D. A.; Hanquet, G. J. Org. Chem. 2006, 71, 4854-4861.

  14. Kibdelone C – 1st Fragment Synthesis ? Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  15. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  16. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  17. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  18. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Gassman, P. G.; Singelton, D. A.; Wilwerding, J. J.; Chavan, S. P. J. Am. Chem. Soc. 1987, 109, 2182-2184.

  19. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  20. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  21. Kibdelone C – 1st Fragment Synthesis ? Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  22. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  23. Kibdelone C – 1st Fragment Synthesis ? Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  24. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  25. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515.

  26. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Li, J.; Chen, X.; Burgett, A. W. G.; Harran, P. G. Angew. Chem., Int. Ed. 2001, 40, 2682-2685. Otera, J.; Danoh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307-5311.

  27. Kibdelone C – 1st Fragment Synthesis Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511-2515. Li, J.; Chen, X.; Burgett, A. W. G.; Harran, P. G. Angew. Chem., Int. Ed. 2001, 40, 2682-2685. Otera, J.; Danoh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307-5311.

  28. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Lebar, M. D.; Baker, B. J. Tetrahedron Lett. 2007, 133, 9952-9955.

  29. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Barloy-Da Silva, C.; Pale, P. Tetrahedron: Asymmetry 1998, 9, 3951-3954.

  30. Kibdelone C – 2nd Fragment Synthesis ? Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Soucy, R. L.; Kozhinov, D.; Behar, V. J. Org. Chem. 2002, 67, 1947-1952. Shimada, K.; Kaburagi, Y.; Fukuyama, T. J. Am. Chem. Soc. 2003, 125, 4048-4049.

  31. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Soucy, R. L.; Kozhinov, D.; Behar, V. J. Org. Chem. 2002, 67, 1947-1952. Shimada, K.; Kaburagi, Y.; Fukuyama, T. J. Am. Chem. Soc. 2003, 125, 4048-4049.

  32. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

  33. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Bal, B. S.; Childers, W. E.; Pinnick, H. W. Tetrahedron 1981, 37, 2091-2096. Lindgren, B. O. et al. Acta Chem. Scand. 1973, 27, 888-890.

  34. Kibdelone C – 2nd Fragment Synthesis ? Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

  35. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Johansson, R.; Samuelsson, B. J. Chem. Soc., Chem. Commun. 1984, 2371-2374.

  36. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Johansson, R.; Samuelsson, B. J. Chem. Soc., Chem. Commun. 1984, 2371-2374.

  37. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Wei, H.-X.; Timmons, C.; Farag, M. A.; Paré, P. W.; Li, G. Org. Biomol. Chem. 2004, 2, 2893-22896.

  38. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Wei, H.-X.; Timmons, C.; Farag, M. A.; Paré, P. W.; Li, G. Org. Biomol. Chem. 2004, 2, 2893-22896.

  39. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Maiti, D.; Buchwald, S. L. J. Org. Chem. 2010, 75, 1791-1794.

  40. Kibdelone C – 2nd Fragment Synthesis Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Johnson, C. R.; Tait, B. D.; Cieplak, A. S. J. Am. Chem. Soc. 1987, 109, 5875-5876.

  41. Kibdelone C – Combining two fragments Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

  42. Kibdelone C – Combining two fragments Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

  43. Kibdelone C – Combining two fragments Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955. Fillion, E.; Fishlock, D. Org. Lett. 2003, 5, 4653-4656. Xy, F.; Armstrong, J. D.; Zhou, G. X.; Simmons, B.; Hughes, D.; Ge, Z.; Grabowski, E. J. J. Am. Chem. Soc. 2004, 126, 13002

  44. Kibdelone C – End Game Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

  45. Kibdelone C – End Game • Asymmetric Total synthesis of Kibdelone C : • 19 steps (LLS) 36 steps total from commercial SM • Lots of redox steps! Sloman, D. L.; Bacon, J. W.; Porco, J. A., Jr. J. Am. Chem. Soc. 2011, 133, 9952-9955.

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