Burke Group
 |
|
Home
Research
|
Phorboxazole B
The total synthesis of phorboxazole B was
completed in July 2006 by Team Phorboxazole, lead by the now Dr. Brian Lucas
Ph.D. Since the discovery of
the cytotoxic macrolide phorboxazoles by Molinski in 1995, considerable
effort has been directed toward their total synthesis. Phorboxazole A and its C13 epimer,
phorboxazole B, exhibit exceptional cytostatic activity; they have shown a
mean GI50 value of <1.6 x 10-9 M in vitro against the NCI panel
of 60 tumor cell lines. In addition, the phorboxazoles
are believed to operate by a unique mode of action: phorboxazole A induces
S-phase arrest in Burkitt lymphoma cells yet shows no inhibition of tubulin
polymerization or interference with microtubular stability. From a synthetic standpoint, the
phorboxazoles present an attractive challenge. They contain a number of interesting structural features,
including 15 asymmetric centers, a 21-membered macrolactone, four diversely
substituted tetrahydropyran rings, two oxazoles and a vinyl bromide. Ref:
Lucas, Brian S.; Luther, Laura M.; Burke, Steven D. Journal of Organic Chemistry 2005, 70, 3757. |
