The Path To Synthesis

What is Taxol?

      Taxol, the brand name of paclitaxel, is a potent anti-cancer drug. It is primarily known for its effectiveness against breast and ovarian cancers. Paclitaxel was first isolated from the bark of the Pacific yew tree in 1967. While strongly active against tumors in the body, its development into a pharmaceutical treatment was hampered by the difficulties in harvesting a large enough supply. To get even a small amount of paclitaxel required a large amount of bark from a very slow-growing tree.

  Sketch of Paclitaxel structure

      The taxol skeleton is composed of four conjoined rings:   an eight-membered ring, a four-membered ring, and two six-membered rings. There are several functional groups attached to this skeleton. The benzoyl group is particularly crucial for maintaining taxol's strong bioactivity.

      The side chain of taxol also holds functional groups that are essential for its anti-tumor activity. An amide-acyl group of some form at the end of the chain is required. The hydroxy group, on the second carbon of the chain is also necessary; an ester that is easily hydrolysed by the body would also work.

Click-and-drag the mouse in the window to rotate the Taxol molecule.

Jmol: an open-source Java viewer for chemical structures in 3D.
http://www.jmol.org

      In the body, taxol will bind to the microtubules that are part of the cell's cytoskeleton. By stabilising these normally flexible constructions, taxol prevents the cell from dividing into two and causes the cell to die. Because cancer cells divide much quicker than normal cells, taxol predominantly attacks tumors. However, other cells, like hair cells or white blood cells, also divide rapidly and are therefore also a casualty of the treatment. Common chemotherapy side effects of hair loss and immune suppression are a result.

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© 2009 Matthew Radcliff and Dr. Joseph Fox
Created with funding provided by
the Camille & Henry Dreyfus Foundation Special Grant Program in the Chemical Sciences
and the National Science Foundation