Taxol partial synthesis

It has been estimated that six 6-inch-diameter trees would have to be sacrificed for enough Taxol to treat one woman suffering from ovarian cancer. Considering that the number of potential patients in the late 1980s numbered approximately 12,000, an eventual limitation of Taxol was possible. Fortunately, the problem was solved in the early 1990s by the partial synthesis of Taxol from a precursor produced in needles and twigs from the more renewable Taxus baccata. 

Because of the limited natural availability of the compound, as discussed in Sect. 14.3, and despite the complexity of the molecule, huge synthetic efforts have been made to achieve the total synthesis of pachtaxel. These endeavours have resulted in many elegant partial or total synthetic approaches [1-3], and these have been reviewed repeatedly [4, 5]. Numerically, by 2010, there were 156 citations in SciFinder related to the synthesis of taxol and 7,875 citations related to the general terms, taxol and synthesis. In addition to total chemical synthesis, the strategy of site-selective transformation of the complex mixture in the natural taxanes, together with enantio- and diastereo-selective transformation of paclitaxel molecular fragments, complete the pallette of selective transformations that have been studied. 

Partial hydrolysis of an oxazoline to produce the hydroxy amide was used extensively in the synthesis of Taxol analogues (Table 8.24 Scheme It is noteworthy that a solution of the amino... 

Mukaiyama has described a total synthesis of taxol wherein pinacol cyclization of a diketone was employed to construct the A ring in good yield (Eq. 3.13) [31J. In this work, partially reduced alcohols and rearranged compounds were the major side products of the titanium-mediated coupling process. 

Occasionally, the level of a terpenoid in its natural source is too low to make commercial extraction feasible. An example is paclitaxel (also known under the trade name, Taxol ) (Figure 1.16) which is produced by the Pacific Yew, Taxus brevifolia. Paclitaxel has been shown to be an effective agent for the treatment of breast and ovarian cancer. However, the level of paclitaxel in the bark of the tree is so low that it would require three mature trees to produce sufficient paclitaxel to treat one patient. Mature, in this case, means several hundred years old. Thus, there are insufficient trees in the world to treat even a small percentage of women with these diseases. Therefore there has been much activity in attempts to produce total or partial i.e. starting from an available analogue) synthesis of paclitaxel. Similarly, there is currently a great deal of research activity in the search for analogues of paclitaxel which would be easier to produce and would retain the anticancer activity. 

The chemistry of natural products encompasses their isolation, structure elucidation, partial and total synthesis, elucidation of their biogenesis, and the biomi-metic synthesis of N. p. Major breakthroughs in analysis were, e.g., the structural clarifications of morphine, lignin, insulin, estrones, and cholesterol as well as the elucidation of the biosyntheses of terpenoids, morphine, penicillin, chlorophyll, and vitamin B 2. Major advances in synthetic chemistry were, e.g., the total syntheses of camphor, hemin, quinine, saccharose, tropine, stryehnine, chlorophyll, vitamin B 2, erythromycin, taxol and palytoxin. Numerous N. p. of the so-ealled ehiral pool are used as starting materials for the synthesis of optically active compounds or serve (in the form of their derivatives) as catalysts for enantioselective syntheses. 

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