1. Marine Natural Products, Nature’s Medicine Chest California State University, Stanislaus Chad Stessman

2. Outline Natural Products from Marine Sponges What are natural products Why look at sponges How sponges are investigated Synthetic Work on Dolastatin 11 Synthetic Work to Synthesis of Dolastatin 11

3. What are Natural Products Chemicals isolated from living things, plants, animals or micro-organisms. Usually non-essential for life for the source organisms

4. Chemistry

5. Biology Medicine Oceanography Geology

6. Hippocrates 200 BC Ancient Pain Reliever Galen 2 nd century AD Willow tree could be used to reduce fever and pain

7. 1832 German Chemist Discovers Salicin causes The fever reduction and Pain relief Salicin Salicyclic acid Salicyclic acid was created and found to have the same effects as salicin

8. 1897 Felix Hoffman, a chemist at Bayer, developed Acetasalicyclic acid called it Aspirin Felix Hoffman Aspirin

9. Other examples of Natural Products Foxglove Madagascar periwinkle Pacific yew Digitalis-heart disease Vinblastine-anticancer Taxol-anticancer

10. Oceans as sources of natural products

11. Prof. Phil Crews Research Group at University of California, Santa Cruz

12. What Are Sponges? Why Study Them? Members of Phylum Poifera The Most Primitive Example of Multiceullar Creatures Sesile Creatures, Soft Bodied, No Organs Filter Feeders, Pump Water Through Oscules

13. Where to collect sponges?

14. Madagascar

15. Collecting sponges

18. Compounds in the sponges are separated based upon solubility in different solvents

19. Separate further with Chromatography

20. Identifying the Compounds

21. Biological Assays

22. pseudopterosin Bryostatin Jasplakinolide

23. University of Arizona, Tucson

24. Dolastatin 11 Majusculamide C Dollabella auricularia Lyngbya majuscula

25. Cell Division and Cytokinesis Blose, Proced. Nat. Acad. Sci. USA 1979 Molecular Biology of the Cell, 3rd Ed.

26. Cytoskeleton Intermediate Filaments Microtubules Polymer of Tubulin Microfilaments Polymers of Actin

27. Site of Anti-Microfilament Action Swinholide A Tolytoxin Cytochalasin B Phalloidin Jasplakinolide

28. Problem with the Natural Source 3500 lbs Sea hares 2.5 grams 1/100th 25 mg of dolastatin 11

29. Problem with the Natural Source 3500 lbs Sea hares 2.5 grams 1/100th 25 mg of dolastatin 11

31. Analogs of Dolastatin 11

32. Conclusions Natural Products can be valuable new drugs Oceans can also be rich sources of new natural products Natural products can also be made from more readily available starting materials