Enantioselective Total Syntheses of Manzamine A and Related Alkaloids

1. Enantioselective Total Syntheses of Manzamine A and Related Alkaloids John M. Humphrey, Yusheng Liao, Amjad Ali, Tobias Rein, Yue-Ling Wong, Hui-Ju Chen, Anne K. Courtney, and Stephen F. Martin* Presented by: Jixin Liu

2. Stephen F. Martin M. June and J. Virgil Waggoner Regents Chair in Chemistry now at The University of Texas at Austin B.S. University of New Mexico (1968) Ph.D. Princeton University (1972) with Professor Edward C. Taylor Postdoctoral work at the University of Munich with Professor Rudolf Gompper, and further work with Professor George Büchi at the MIT. Known for his work in alkaloid synthesis; Current research is directed toward the syntheses of natural and unnatural products that are of biological or structural interest J. AM. CHEM. SOC. 2002, 124, 8584 8592

3. Manzamine A, a structurally unique β-carboline alkaloid derived from marine sponge Haliclona sp., exhibiting a high level of antimalarial activity in vivo when tested in Plasmodium berghei (ANKA)-infected mice.

4. Manzamine A

5. 3D

7. Manzamine A

8. Retro synthesis

9. Key Steps • Intramolecular Diels Alder reactions to produce the tricyclic ABC core of the manzamines • Ring-Closing Metathesis of E ring

10. Key steps D-A reaction

11. Key steps Ring-Closing

12. Ring Closing

13. Ring-Closing

14. Forward Synthesis

15. Forward Synthesis

16. Forward Synthesis

17. Forward Synthesis

19. Forward Synthesis

20. Forward Synthesis

22. Pictet-Spengler

23. Conclusion • The longest linear sequence was 21 steps • The concise approach highlights a novel strategy for assembling the tricyclic ABC ring core by a Diels Alder reaction. • 13- and 8-membered heterocyclic rings were synthesized via RCM. Thank you!