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

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

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

Chemistry

Biology Medicine Oceanography Geology

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

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

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

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

Oceans as sources of natural products

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

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

Where to collect sponges?

Madagascar

Collecting sponges

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

Separate further with Chromatography

Identifying the Compounds

Biological Assays

pseudopterosin Bryostatin Jasplakinolide

University of Arizona, Tucson

Dolastatin 11 Majusculamide C Dollabella auricularia Lyngbya majuscula

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

Cytoskeleton Intermediate Filaments Microtubules Polymer of Tubulin Microfilaments Polymers of Actin

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

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

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

Analogs of Dolastatin 11

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