Taxol, extraction

The need to carry out extensive surveys of Taxus species for their taxol content and to monitor taxol in clinical studies has spurred efforts to develop new analytical methods for taxol purification. Solvent extraction methods are always inexpensive and easy to handle. Different solvent systems started from very nonpolar solvents (e.g., n-hexane) [6] senupolar system (chloroform and acetone or combination of dichloromethane methanol) [7] and very polar system (methanol or ethanol alone or with H2O) [7] have been employed for extraction of taxoids from bark or leaves of Taxus species. To date only chromatographic methods have been reported. Sadeghi-aliabadi et al. in their studies to find an optimized solvent for taxol extraction indicated that the solvent 100 % acetone is the best solvent to extract higher amount of taxol fi om Taxus baccata needles. They confirmed their results by HPLC, ESI-LCMS, and biological cytotoxic evaluations of extracted compounds [8]. 

Sadeghi-aliabadi H, Asghari G, Mostafavi SA, Esmaeili S (2009) Solvent optimization on Taxol extraction from Taxus baccata L, nsing HPLC and LC-MS. Daru J Pharm Sci 17(3) 192-198... 

F.14 Paclitaxel, which is extracted from the Pacific yew tree Taxus brevifolia, has antitumor activity for ovarian and breast cancer. It is sold under the trade name Taxol. On analysis, its mass percentage composition is 66.11% C, 6.02% H, and 1.64% N, with the balance being oxygen. What is the empirical formula of paclitaxel ... 

Another drug is taxol, which is extracted from the bark of the Pacific yew tree, Taxus brevijolia. Unlike colchicine and the vinca alkaloids, taxol binds tightly to microtubules and stabilizes them against depolymerization by Ca. It also enhances the rate and yield of microtubule assembly, thereby decreasing the amount of soluble tubulin in the cytosol pool. Again, the overall effect of taxol is to arrest dividing cells in mitosis. Taxol is used in cancer chemotherapy. 

Since the discovery of the anticancer potential of Taxol , a complex compound isolated from the bark extract of the Pacific yew tree, more than 20 years ago, there has been an increasing demand for the clinical application of this compound. First, the promising results of the 1991 clinical trials in breast cancer patients were announced, and soon after Bristol-Myers-Squibb trade-marked the name Taxol and used it as an anticancer drug. At that point, the only source of the drug was the bark of the endangered yew tree. Fortunately, it was soon discovered that a precursor of Taxol could be obtained from an extract of the tree needles instead of the bark. 

Paclitaxel (Taxol, Bristol-Myers Squibb) is a chemotherapy drug for ovarian cancer, breast cancer, and certain lung cancers. It was discovered by the US National Cancer Institute in the 1960s. Originally, it was extracted from the bark of the North American yew tree (Taxus brevifo-lia). Clinical tests had necessitated the harvesting of the bark, and this method damaged the trees irreversibly. 

The metabolism of taxol by Eucalyptus perriniana cell suspension cultures has been recently reported to induce hydrolyses of ester bonds at C-13, C-10 and C-2 [222]. At this moment only very few data have been published about the microbial metabolism of taxoid compounds only site specific hydrolyses of acyl side-chains at C-13 or C-10 by extracellular and intracellular esterases of Nocar-dioides albus SC13,911 and N. luteus SC13,912, respectively, have been reported [223]. On the other hand, Hu et al. [224-226] have recently described some fungal biotransformations of related natural taxane diterpenes extracted from Chinese yews or their cell cultures, in order to obtain new active substances or precursors for hemisynthesis. The taxadiene 145, a 14 -acetylated derivative... 

Taxol was the most triumphant new anticancer drug developed in the last few decades. It resulted from a drive to screen thousands of synthesized compounds and plant extracts, financed by the National Cancer Institute (Georg et al. 1994, Suffness 1995, Goodman and Walsh 2001). Taxol is extracted from the bark of the Pacific yew tree, or Taxus brevifoli, found in the Pacific Northwest, and has been proven effective against intractable breast and ovarian cancers. It is now produced by semi-synthetic methods from the needles of the common ornamental tree English Yew, or Taxus baccata. We will discuss taxol in greater detail in Chapter 2. 

P-1534 leukemia, the Walker 256 carcinosarcoma, and the P388 leukemia. He also worked on isolation by extraction of 12 kg of Pacific yew bark with ethanol, followed by partition of the ethanol extract between chloroform and water. In his first publication in 1967, about 0.5 g of taxol was isolated from 12 kg of air-dried stem and bark from T. brevifolia, and the yield was about 0.004%, or 40 ppm. 

Since the bottleneck on the clinical trial for taxol was in the supply, the NCI turned in 1989 to industrial partners, and issued a request for a Cooperative Research and Development Agreement, and selected Bristol-Myers Squibb (BMS) in 1991 as the partner in taxol development. BMS would take responsibility for the short-term supply of taxol, and NCI would sponsor research to deal with long-term supply. BMS collected 750,000 lbs of dried T. brevifolia bark from 38,000 trees during the 1991 growing season, sufficient to yield 25 kg of pure taxol to treat about 12,000 cancer patients. Hauser Chemical Research of Boulder, Colorado, was overseeing collection of yew bark and processing of the bark to extract taxol. BMS prepared the final dosage formulation and delivered it to the NCI for use in clinical studies. 

Extraction Restoration of Taxol source switch Lamp oil from whales to... 

Plant-based products obtained by direct extraction from a native producer, or by semi-synthesis (e.g. taxol) No Yes No... 

The diterpenoid taxol (Figure 1.12) was first isolated from the pacific yew tree (Taxus brevifolia) in the late 1960s. Its complete structure was elucidated by 1971. Difficulties associated with the subsequent development of taxol as a useful drug mirror those encountered during the development of many plant-derived metabolites as drug products. Its low solubility made taxol difficult to formulate into a stable product, and its low natural abundance required large-scale extraction from its native source. 

The taxanes are a group of polycyclic diterpenes produced by various species of trees (such as yew) and are most commonly known as the potent anticancer drug paclitaxel (Taxol). The extraction process is costly. 

Taxol has had a most unusual clinical development history. As with many natural products that have been discovered to provide therapeutic benefit to humans, it was the extract of a plant that provided the first hint of the oncological potential of this product. Natural product chemists typically subject purified plant extracts to screening for therapeuhc achvity. In 1963, an extract of the bark of the Pacific yew tree (Taxus brevifolia (Figure 7.2) showed anti-tumor activity. This early work was done by Monroe Wall and Monsukh Wani of the Research Triangle Institute (RTI) under the auspices of the National Cancer Institute (NCI) [3]. 

From Extraction of Taxol from Pacific Yew Tree Bark to Semi-SYnthetic Taxol 1147... 

With the successful development and commercial manufacture of semi-synthetic Taxol , tile destruction of the Pacific yew tree forests was halted. However, this successful move away from an essentially non-renewable source (extraction of the Pacific yew tree bark) to a renewable source (harvested European yew tree leaves and twigs to obtain 10-DAB, followed by syntliettc transformation to Taxol ) still presented significant environmental challenges. The use of 13 different solvents. 

Ritter, S.K. (2004) Chem. Eng. News, 82 (27), 4. Also Development of Green Synthesis for Taxol Manufacture via Plant Cell Fermentation and Extraction submitted for 2004 EPA Greener Synthetic Chemistry award, http //www. epa.gov/greenchemistry/pubs/pgcc/ winners/gspa04.html (accessed May 2009). 

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