Total Synthesis of (-)-Conophylline and (-)-Conophyllidine

1. Total Synthesis of (-)-Conophylline and (-)-Conophyllidine Tohru Fukuyama* @ University of Tokyo Angew. Chem. Int. Ed. 2011, 50, 4884 –4887 Song jin 2011-06-25 Gong Group Meeting

2. ＊(-)-Conophylline , isolated from Tabernaemontana divaricata(狗牙花) in 1992. ＊has been found to induce beta-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured fetal rat pancreatic tissue

5. ＊sterically lesshindered ＊tin-mediated indole synthesis ＊bubbling of argon gas for 10 min, then reflux

6. ＊tin-mediated indole synthesis Fukuyama, J. Am. Chem. Soc. 1994,116, 3127

7. Stille coupling

8. Mistunobu reaction Appel Reaction

10. ＊Polonovski–Potier reaction

11. ＊Polonovski–Potier reaction

12. ＊ Stabilizing the carbocation ＊ ＊ Husson, J. Org. Chem. 1982, 47, 803-811

15. Thank You

18. Mitsunobu reaction betaine intermediate Nucleophile: COOH, HN3, Phenol, sulfonamide pKa ( betaine intermediate) ～13 the nucleophile must have a pKa less than 15

19. Appel reaction