1. Total Synthesis of Zoanthamine Alkaloids郭蕊
Miyashita, M., et al. Acc. Chem. Res., 2012, ASAP.
Stoltz, B.M., et al. Angew. Chem. Int. Ed. 2008, 47, 2365

2. Natural Products Isolated from the Zoanthids
PGA2
Zoanthoxanthin
Zoanthoxanthin

3. Zoanthamine Alkaloids: Isolation and Biological Activity

Isolation: Rao and Faulker, 1984 off the coast of India
Biological activity: Inhibits ear inflammation in mice
Norzoanthamine:

Isolation: Uemura, 1995 from the coast of islands south of Japan

Biological activity:
Prevents osteoporosis in vivo in ovarieoctimized mice

Cytoxicity against P388 murine leucemia cells

Inhibits human platelet aggregation
Zoanthenol:

Isolation: Norte, 1996 in the Canary Islands

Biological activity: Inhibits human platelet aggregation
Rao, C. B.; Faulkner, D. J., et al. J. Am. Chem. Soc. 1984, 106, 7983.
Uemura, D., et al. Heterocycl. Commun. 1995, 1, 207
Norte, M., et al. Tetrahedron, 1999, 55, 5539.

4. Synthetic Efforts Towards Norzoanthamine
Total synthesis:
• Miyashita, Norzoanthamine-2004
Partial synthesis:
• Tanner
• Williams
• Uemura
• Stoltz
• Theodorakis
• Kobayashi
Miyashita, M., et al. Science, 2004, 305, 495.

5. Retrosynthetic Analysis of Norzoanthamine
41 steps, 3.5% overall yield (average of 92% yield per step)
• Key steps:
• IMDA to set stereochemistry of the BC rings
• Use of kinetic isotope effect for installation of alkyne
• Bis-aminoacetalization for the construction of the DEFG rings

6. Synthesis of the ABC Ring System

7. Chugaev Elimination

8. Hydrosilylation reaction in the presence of Wilkinson’s catalyst
Ojima I., et al. Organometallics, 1982, 1, 1390
Katsumura protocol
Katsumura K., et al. Tetrahedron Lett. 1985, 38, 4625

9. Key Intramolecular Diels-Alder Reaction

10. Methylation

11. Trost protocol
Trost B. M., et al. Tetrahedron Lett. 1984, 25, 173

13. The Kinetic Isotope Effect

14. Construction of the DEFG Rings

15. Ito-Saegusa method
Ito Y., Hirao T., Saegusa T., J. Org. Chem. 1978, 43, 1011

16. Completion of Norzoanthamine

17. Total Synthesis of Zoanthamine
Miyashita, M., et al. Chem.Eur. J. 2009, 15, 6626

18. Total Synthesis of Zoanthenol
Miyashita, M., et al. Chem. Asian J. 2011, 6, 922
Miyashita, M., et al. Angew. Chem., Int. Ed. 2009, 48, 8905