1. Total Synthesis of (+)-Fastigiatine
Gretchen Peters
February 10, 2011

2. Shair Research Group Total synthesis and chemical biology
Focus of syntheses: “naturally occurring complex molecules that challenge the state- of-the-art of organic synthesis”
Complexes that are unique structurally and biologically

3. Lycopodium alkaloids Found in plants (clubmosses)
(-)-himeradine A
lycodine
(+)-fastigiatine
Found in plants (clubmosses)
Members have been found to have cardiovascular and neuromuscular effects
Used for homeopathic remedies

4. Retrosynthesis
1,4 Addition
Mannich
Condensation

5. Protection 2 1

6. Cuperate Addition 2 3

7. Alkylation, Decarboxylation4 3 5

8. Addition of Li-enolate5 7 6

9. Intramolecular Aza-Wittig6 7

10. Reactive Amine Wanted to remove protecting group and induce addition
Free amine too reactive
Added on to a,b unsaturated ketone to form five-membered ring 7

11. Acid catalyzed cyclization7 8 9

12. Mannich Reaction 9 10

13. Conclusions First synthesis of (+)-fastigiatine
15 step synthesis with 30% overall yield

14. Acknowledgements
Chem 647 classmates
Dr. Davis