text: Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew (Taxus brevifolia). Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential.
  The paclitaxel molecule consists of a tetracyclic core called baccatin III and an amide tail. The core rings are conveniently called (from left to right) ring A (a cyclohexene), ring B (a cyclooctane), ring C (a cyclohexane) and ring D (an oxetane).
  The paclitaxel drug development process took over 40 years. The anti-tumor activity of a bark extract of the Pacific yew tree was discovered in 1963 as a follow-up of a US government plant screening program already in existence 20 years before that. The active substance responsible for the anti-tumor activity was discovered in 1969 and structure elucidation was completed in 1971. Robert A. Holton of Florida State University succeeded in the total synthesis of paclitaxel in 1994, a project that he had started in 1982. In 1989 Holton had also developed a semisynthetic route to paclitaxel starting from 10-deacetylbaccatin III. This compound is a biosynthetic precursor and is found in larger quantities than paclitaxel itself in Taxus baccata (the european yew). In 1990
  Bristol-Myers Squibb bought a licence to the patent for this process which in the years to follow earned Florida State University and Holton (with a 40% take) over 200 million US dollars.