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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 thesource organisms
Chemistry
Chemistry
Biology
MedicineOceanography
Geology
Hippocrates 200 BC
Ancient Pain Reliever
Galen 2nd century AD
Willow tree could be used to reduce
fever and pain
1832 German ChemistDiscovers Salicin causes The fever reduction and
Pain relief
O O
OH
OH
OH
OHOH
Salicin
Salicyclic acid
OH
O OH
Salicyclic acid was createdand found to have the same
effects as salicin
1897 Felix Hoffman, a chemist at Bayer, developedAcetasalicyclic acid called it Aspirin
Felix Hoffman Aspirin
O
O
O
OH
CH3
Other examples of Natural Products
FoxgloveMadagascar 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 spongesare separated based uponsolubility in different solvents
Separate further with Chromatography
Identifying the Compounds
Biological Assays
pseudopterosin
Bryostatin
Jasplakinolide
University of Arizona, Tucson
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
O
1
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
O
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
MicrotubulesPolymer of Tubulin
MicrofilamentsPolymers of Actin
Site of Anti-Microfilament Action
Swinholide A
Tolytoxin
Cytochalasin B
PhalloidinJasplakinolide
Problem with the Natural Source
3500 lbsSea hares 2.5 grams
1/100th
25 mg of dolastatin 11
Problem with the Natural Source
3500 lbsSea hares 2.5 grams
1/100th
25 mg of dolastatin 11
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
O
Ala Map
Hmp
Gly-2
N-Me-Leu
Gly-1N-Me-Val
N,O-diMe-Tyr
Ibu
12
69
11
14
17 2023
26
29
Analogs of Dolastatin 11
OO
N
O
O
NH
N
O
HN
N
O O
MeO
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
O
R-Ala
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
O
N
NNH
N
O
O HN
O
O
O
O
NH
OHN
OHN
O
O
MeO
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 morereadily available starting materials