Yew tree

Ephedrine also oeeurs in the leaves of the yew tree [Taxus baccata) and in Sida rhombifolia Linn, whilst Stockman s cathine from Catha edulis Forsk has been shown by Wolfes to be d-nor- -ephedrine. Ghosh, Chopra and Dutt state that the bark of Moringa pterygosperma Gaertn. contains two alkaloids similar to ephedrine in pharmacological action. The more active of the two, moringinine, is amorphous the other is a liquid but jdelds a crystalline hydrochloride, C,H. HCl, m.p. 254-4°, + 1-8°, a picrate, m.p. 195°, and an aurichloride, m.p. 170-8°. 

A new antitumor drug, taxol, has been isolated from the bark of Taxus brevifolia, the Pacific yew tree. Like vinblastine and colchicine, taxol inhibits cell replication by acting on microtubules. Unlike these other antimitotic drugs, however, taxol stimulates microtubule polymerization and stabilizes microtubules. 

The total synthesis of taxol (52) has been described in Chapter 34. Clearly, total synthesis cannot hope to meet the demand for taxol at the present time, and supplies are currently procured by semisynthesis. This approach uses baccatin III (derived from yew tree needles) and the C-13 side chain 51, made synthetically (Scheme 13). A practical synthesis of the side chain is necessary,... 

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

Polvoras Negras (Span for BlkPdrs). Fairly detailed description of Span method of manuf is given by Sancho (Ref, p 264). The sources of the charcoal used were stems of hemp (tallos de canamo), of flax (lino), of oleander (adelpha), of yew-tree (tejo), etc. Following, in Table 1, are given typical compns of some Span BlkPdrs... 

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. 

There are natural targets whose syntheses have important practical applications. For example, paclitaxel (marketed as Taxol by Bristol-Myers Squibb) is an anticancer compound originally isolated from the bark of a species of yew tree, but for a long time it seemed that natural sources would not be sufficient to meet the need. Consequently, many chemists developed synthetic approaches to paclitaxel from readily available materials, although these are not yet fully practical for manufacturing. The quest continues, and a semisynthetic route has been developed starting with a compound isolated from yew needles that can be harvested without destroying the tree. An alternative approach has employed plantcell cultures in bioreactors to produce paclitaxel from yew needles (see Chapter 7 for discussion of related matters). 

The answer is c. (Hardman, pp 1260—1262.) Paclitaxel is a large structural molecule that contains a 15 membered taxane ring system. This anti cancer agent is an alkaloid derived from the bark of the Pacific yew tree. Its chemotherapeutic action is related to the microtubules in the cell. Paclitaxel promotes microtubule assembly from dimers and causes microtubule stabilization by preventing depolymerization. As a consequence of these actions, the microtubules form disorganized bundles, which decreases... 

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. 

The advantages of MAE are short extraction times (10 min), extraction of many samples at one time (up to 14, depending on the system), and less organic solvent consumed. In one recent study [29], MAE was used to extract paclitaxel from Iranian yew trees. The needles of the tree were air-dried and ground. The needles were covered with methanol-water and placed in the MAE apparatus. Extractions took 9-16 min. The extracts were filtered and analyzed by HPLC. Further optimization of the method resulted in less than 10% RSDs for precision and greater than 87% recovery. The overall benefits of the MAE method are reduced extraction times (15-20 min versus 17 h), minimal sample handling, and 75-80% reduction in solvent consumption [29]. 

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. 

Environmental groups objected to this practice, and many demonstrations were staged. A solution was eventually found when the needles of the European yew tree Taxus baccata) provided a source for the paclitaxel precursor without destroying the bark. 

Early production of 1 kg of paditaxel required extraction from about 13,000kg of the Pacific yew tree bark. This process was refined, and pacli-taxel is now produced by a semisynthetic route. The starting material, 10-deacetyl baccatin 111 (10-DAB), is obtained from the needles of Taxus baccata (European yew) or T. wallichiana (Himalayan yew). The yield is around 1000 kg of needles to produce 1kg of 10-DAB. 

Wancer is one of the leading causes of death in Canada. It is a disease in which cells mutate and grow at uncontrolled rates, disrupting the body s normal functions. TAXOL , shown at the bottom of the page, is an organic compound that is found in the bark of the Pacific yew tree. After many tests and reviews, TAXOL was approved for use in treating ovarian cancer. 

The bark of a large yew tree yields only enough TAXOL for a single treatment. However, cancer patients require repeated treatments over a long period of time. Working in a laboratory, chemists found the first solution to this problem. They developed several different methods to make, or synthesize, TAXOL , from simple, widely available chemicals. Unfortunately, these methods are expensive and time-consuming. 

The needles and twigs of the European yew contain 10-deacetylbaccatin III, shown at the bottom of the page. A few reaction steps can transform 10-deacetylbaccatin III into TAXOL . Instead of destroying an entire Pacific yew tree for a single treatment of TAXOL , scientists can now use the needles from a European yew. The parent tree is not harmed. 

Taxol i is a naturally occurring substance isolated from the Pacific yew tree Taxus brevifolia), which has been approved for clinical treatment of cancer patients. Taxol enhances polymerization of tubuhn and the consequent formation of stable microtubules, inhibiting cellular mitosis. 

Q48 was synthesised to mimic the nerve-blocking activity of cocaine Q49 is indicated for dementia in Alzheimer s disease Q50 was originally derived from the bark of the yew tree... 

Taxol is an anticancer drug obtained from the Pacific yew tree (Taxuxbrevifolia). (Mix/ Phanie/Photo Researchers, Inc.)... 

Hopes for using paciltaxel in the treatment of cancer were dampened, however, by the fact that the Pacific yew tree is a slow-growing, threatened tree. Its harvest for the collection of paciltaxel from its bark would almost certainly have led to the tree s extinction. Instead, researchers turned to the obvious alternative, characterization of the chemical structure of paciltaxel and its chemical synthesis. That task was a challenge, however, because of the complex structure of the paciltaxel molecule. After more than a decade of research, however, the task was accomplished Researchers achieved a successful method for the synthesis of the compound in the laboratory. In 1992, the FDA approved paciltaxel for use against cancers that had failed to respond to other treatments. By this time, the compound was... 

Formidable chemical obstacles stood in the way of clinical development of these agents derived from natural products, notably in formulation of very poorly soluble compounds for intravenous infusion and in manufacture of bulk drug. For a time, production of Taxol from the bark of the Pacific Yew tree aroused public controversy, which became a story of nature and politics in pursuit of an anti-cancer drug [22]. 

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. 

There are several books on the history of the development of taxol, which is one of the most remarkable stories in product development. In fact, it inspired the 1992 motion picture Medicine Man, starring Sean Connery as a research botanist looking for a cancer cure in the Brazilian rain forest. For a time, it became a moral drama pitting the needs of patients of intractable ovarian and breast cancer against the passions of environmentalists to preserve an obscure Pacific yew tree. Suffness and Wall are two of the principals in this story, and they wrote (1995) It [Taxol] is not an obvious winner till the very end, and there were a number of times till the very end when it seemed highly likely that it would not be put into development at all, or that once it had been accepted, it would be dropped. More than 30 years passed between the discovery of taxol, with its potential as an anticancer drug, and its approval by the Food and Drug Administration (FDA) for clinical use. 

---