2. Isolation:
Gunasekera (1990)
Yield:
0.002wt% (7 mg/454 g of sponge)
Biological Activity:
Discodermia dissoluta
Immunosuppression
Antifungal
Microtubule Stabilization (MTS agent)
Important Profiles:
• Acts more faster and powerful than any other MTS agents.
Cancer Cell and
• Effective against multi-drug (include Taxol) resistant cell lines. Its Apoptosis
• High water solubility (100-fold greater than Taxol)
• Unique action mechanism, etc…
Very attracted compound !!!
Isolation: JOC 1990, 55, 4912. For action of mechanism, see: ACIE 1998, 37, 2014.
3. 1990 Gunasekera Isolation
1993 Schreiber First total synthesis ((–)-form)
Established absolute configuration
1994 Schreiber First natural (+)-enantiomer synthesis
1995 Smith (–)
1997 Myles (–)
1998 Marshall (+)
1999 Smith Gram-scale synthesis
2000 Paterson Novel approach
2002 Paterson 2nd generation
2003 Smith 2nd generation
2003 Novartis Process synthesis
Phase I clinical trials
2005 Panek (+)
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12. What are most effective?
1. Aldol
2. Allylboronate/allylborane addition to aldehyde
3. Ireland-Claisen
4. Diels-Alder
Marshall’s concept: chiral allenylmetal methodology (variant of 2)
JOC 1998, 63, 817
