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

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 http://www.chem.harvard.edu/research/faculty/matthew_shair/research/research.html

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 http://findarticles.com/p/articles/mi_g2603/is_0004/ai_2603000497/

Retrosynthesis 1,4 Addition Mannich Condensation

Protection 2 1

Cuperate Addition 2 3

Alkylation, Decarboxylation 4 3 5

Addition of Li-enolate 5 7 6

Intramolecular Aza-Wittig 6 7

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

Acid catalyzed cyclization 7 8 9

Mannich Reaction 9 10

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

Acknowledgements Chem 647 classmates Dr. Davis