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Needing large quantities of taxol in order to gather statistically significant data about its efficacy in the human body, scientists looked for original sources other than the Pacific yew tree. They also looked for material that could quickly and cheaply be converted into taxol.
In 1981, Pierre Potier showed that a similar compound, 10-deacetylbaccatin-III (10-DAB), could be isolated in large quantities from the needles of the much more common English yew shrub. Harvesting evergreen needles allowed for a regular and sustainable supply of the compound; provided, of course, that a route could be found to convert 10-DAB into taxol. 10-DAB already incorporates the complicated tetracycline (four-ring) skeleton of taxol. The only component missing (aside from the side chain) is the acetyl group on the tenth carbon (located at the top of the figure). When the acetyl group is present, the compound is known as baccatin-III.
By 1989, Robert Holton had developed a method to add both the acetyl group to 10-deacetylbaccatin-III and the side chain, resulting in the first practical semi-synthesis of taxol. Because the synthetic pathway started with a “pre-cursor” molecule, and not from simple building blocks, it is not considered a “total synthesis.” |
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