EASY WAY OF TAXOL TOTAL SYNTHESIS

TOTAL SYNTHESIS OF TAXOL

BY NILESH GHUTE

TAXOL MODE OF ACTION

Horwitz and coworkers showed taxol’s unique biological action, which includes promotion of microtubule formation and microtubule stabilization (Horwitz et al Nature, 1979, 277, 665). Taxol kills cells by a different mechanism than other drugs. During cell mitosis, a cellular protein called tubulin undergoes a reversible polymerization to form structures known as microtubules, which are required for the formation of the mitotic spindle. Taxol binds to the microtubules, stabilizing them, and altering the tubulinmicrotubule equilibrium. As a result, the cells cannot undergo normal mitosis and they die. In 1992, taxol was approved by US FDA for the treatment of ovarian, breast, Lung cancer and melanoma.

HISTORY

Ancient times-Julius Caesar mentioned in his book “Gallic Wars” that Catuvolcus, a chieftain committed suicide by taking extracts from yew tree.

In the early 1960s, the National Cancer Institute (NCI) in the United States initiated a programme of biological screening of extracts taken from a wide variety of natural sources.

One of these extracts was found to exhibit marked anti tumor activity against a broad range of rodent tumors.

Several reports on the uses of such extracts as poison or as a cancer-healing folk medicine.

The modern History (1962)-joint project between US Dept. of Agriculture and the National Cancer Institute aimed for the discovery of new anticancer agents.

Isolation- bark of yew tree (Taxus brevifolia).

In 1971-a diterpenoid structure was established by X-ray crystallography.

TOTAL SYNTHESIS

Greek word synthesis = the process of putting together.

A construction of nature’s molecules in the laboratory from atoms and/or simple molecules-a process often known as total synthesis is one of the most demanding human practices.

Why total synthesis?

ANSWER-The presence of active components in the nature are very low. e. g. It has been estimated that the sacrifice of one 100-year-old yew tree would give only 300 mg of Taxol, just enough for single dose for a cancer patien