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
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
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.
Manzamine A
3D
Manzamine A
Retro synthesis
Key Steps
• Intramolecular Diels Alder reactions to
produce the tricyclic ABC core of the
manzamines
• Ring-Closing Metathesis of E ring
Key steps
D-A reaction
Key steps
Ring-Closing
Ring Closing
Ring-Closing
Forward Synthesis
Forward Synthesis
Forward Synthesis
Forward Synthesis
Forward Synthesis
Forward Synthesis
Pictet-Spengler
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.