Paclitaxel semi-synthetic production from

It has been suggested that Taxol exerted its activity by preventing depolymerization of the microtubule skeleton. Clinical use of pachtaxel includes a lot of solid tumors with best results in ovarian and breast cancers. Extraction of paclitaxel from the yew bark was quite difficult three trees for Ig of drug (one cure of chemotherapy). This difficulty encouraged the pursuit of semi-synthetic production. 

Early production of 1 kg of paclitaxel required extraction from about 13 000 kg of the Pacific yew tree bark. This process was refined, and paclitaxel is now produced by a semi-synthetic route. The starting material, 10-deacetyl baccatin III (10-DAB) is obtained from the needles of Taxus baccata (European yews) or T. wallichiana (Himalayan yews). The yield is around 1000 kg of needles to produce 1 kg of 10-DAB. 

Plants have also provided a key source of potential cancer treatments. A well-known example is paclitaxel (Taxol ), isolated from the bark of the Pacific yew tree, which has become a blockbuster drug and analogues have also been approved for use that demonstrate improved efficacy (Fig. 1.4) [6]. Taxol also provides an excellent example to illustrate the challenges that remain in total synthesis. Numerous examples of the total synthesis of Taxol have been reported [7-13]. However, the overall yield and the number of steps required means it is not economically viable to synthesise the quantities required for its medicinal application. It is therefore obtained industrially via a semi-synthetic route starting from 10-deacetylbaccatin HI, a biosynthetic precursor, which can be isolated, in much larger quantities than Taxol itself, from the leaves of a different species of yew tree. More recently however, a plant cell fermentation approach has been developed for the industrial production of Taxol. 

The overexpression of the anti-apoptotic protein Bcl-2 in cancer has been associated with resistance to chemotherapeutic agents. The phosphorylation of Bcl-2 is one mechanism by which antimicrotubule agents in clinic such as paclitaxel, taxotere and vinblastine inactivate the Bcl-2 proteins. Many natural products and semi-synthetic molecules are used in clinic for anticancer activity. In this chapter, the importance of the Bcl-2 phosphoiylating molecule from nutraceuticals that shed light on the future development of molecules for chemoprevention and anticancer drugs will be discussed. The roots of Licorice (Glycyrrhiza glabra) have been used in traditional medicine for a variety of... 

---