1. Total Synthesis of Manzamine A and Related Alkaloids
Pavol Jakubec, Alison Hawkins, Wolfgang Felzmann, and Darren J. Dixon*
J. Am. Chem. Soc., 2012, 134, 17482–17485
Speaker: 王湘閔

2. Outline Motivation Introduction Past work Retrosynthesis Synthesis
Conclusion
Summary

3. Motivation

4. Introduction
Isolation: Alkaloids were first isolated from the marine sponge Haliclona sp. in the Okinawa Sea by Higa et al. in 1986.
Biological activities: insecticidal, cytotoxicity, antibacterial, anti-HIV-I, anti-infective, anti-Alzheimer diseases, and anti- malarial activity.
P388 mouse leukaemia cells
(IC50 = 0.07 µg/mL or 2.4 µg/mL)

5. Past work

6. Retrosynthetic Analysis

7. Preparation of homoallylic alcohol 10

8. Synthesis of Electrophile 6
Mechanism:

9. Stereoselective Michael Addition of Key Building Block
Mechanism:

10. Preparation of A-ring via Nitro-Mannich/lactamization cascade
Mechanism:

11. Synthesis of Intermediate 4

12. Preparation of B-ring 19
Mechanism:

13. Synthesis of Key Intermediate 2
Mechanism of Nef Reaction
Mechanism:

14. Completion of the Total Synthesis of Manzamine A, Ircinol A, and Ircinal A

15. Conclusion
Author and co-workers have developed a short and stereoselective synthesis of manzamine A (1) via 18 steps, total yield 1.03 %.
Enol triflate 2 is a synthetically valuable late-stage intermediate.
Key steps:
Stereoselective Michael addition
Nitro-Mannich/Lactamization cascade
Z-selective alkene RCM

16. Summary Paper Author Key Step Steps, yield
J. Am. Chem. Soc. 1998, 120,
Winkler, J.D.
Pictet-Spenglar Cyclization & DDQ oxidation
22 steps, 0.09%
J. Am. Chem. Soc. 1999, 121,
Martin S.F.
Stille/Diels-Alder reaction &
Ring-Closing Metathesis
21 steps, 0.17%
J. Am. Chem. Soc. 2010, 132,
Fukuyama T.
Diels-Alder reaction &
27 steps, 1.7%
J. Am. Chem. Soc. 2012, 132,
Dixon, D.J.
Stereoselective Michael addition
Nitro-Mannich/Lactamization
Z-selective alkene RCM
18 steps, 1.03%

17. Thanks for your attention