Taxol brevifolia

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. 

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 ... 

Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971 93 2325-7. 

A fine example of such a semi-synthesis is the preparation of the anti-cancer drug paclitaxel (Taxol ), a relatively scarce compound from Taxus brevifolia. Here, the natural and better accessible 10-deacetylbaccatin III, isolated from the leaves of Taxus baccata, provides the complicated ring system of paclitaxel, including all substituents with the right stereostructure (Scheme 5.1). In just four reaction steps [5] paclitaxel is obtained from 10-deacetylbaccatin III. 

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. 

Taxol (Paclitaxel) 137, a natural product derived from the bark of the Pacific yew, Taxus brevifolia [213-215], and the hemisynthetic analogue Docetaxel (Taxotere) 138, two recent and promising antitumour agents, have been the matter of extensive in vivo and in vitro animal metabolic studies. The major metabolites of taxol excreted in rat bile [216] were identified as a C-4 hydroxylated derivative on the phenyl group of the acyl side chain at C-13 (139), another aromatic hydroxylation product at the mefa-position on the benzoate group at C-2 (140) and a C-13 deacylated metabolite (baccatin III, 142) the structure of six minor metabolites could not be determined. The major human liver microsomal metabolite, apparently different from those formed in rat [217], has been identified as the 6a-hydroxytaxol (141) [218, 219]. A very similar metabolic pattern was... 

Paclitaxel (21), formerly known as taxol , is a nitrogen-containing diterpenoid compound isolated from the bark of Taxus brevifolia Nutt. (Pacific yew). As an anticancer agent, paclitaxel acts as a tubulin stabilizer and leads to cell cycle arrest.Since paclitaxel was originally isolated from the bark of the slow-growing species, 77 brevifolia, sourcing was a major obstacle in the development of this drug and its introduction into the market.However, as described later in this chapter, this has now been overcome. 

Stierle A, Strobel G, Stierle D, Grothaus P, Bignami G, The search for a taxol-producing microorganism among the endophytic fungi of the pacific yew, Taxus brevifolia, JNat Prod 58 1315-1324, 1995. 

Stierle A, Stierle D, Strobel G, Bignami G, Grothaus P, Endophytic fungi of pacific yew Taxus brevifolia) as a source of taxol, taxanes and other pharmacophores, in Bioregulators for Crop Protection and Pest Control, American Chemical Society, Washington DC, pp. 64—77, 1994. 

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. 

Taxol Terpenoid Ovarian, breast cancer Taxus brevifolia (western yew tree)... 

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. 

Nature has been a potential source of therapeutic agents for thousands of years. An impressive number of modem dmgs have been derived from natural sources. Over the last century, a number of top selling dmgs have been developed from natural products. Anticancer dmg vincristine from Vinca rosea, narcotic analgesic morphine from Papaver somniferum, antimalarial dmg artemisinin from Artemisia annua, anticancer dmg Taxol from Taxus brevifolia and antibiotic peniciUins from Penicillium ssp. are just a few examples. 

N.A. Taxus x media Rehd. T brevifolia Nutt. Taxol, resin.103-95296 Treat cancer, gout, and rheumatism, arthritis. 

Whiterup, . M., S. A. Look, M. W. Stasko, T. J. Ghiorzi, G. M. Muschik, and G. M. Cragg. 1990. Taxus spp. needles contain amounts of taxol comparable to the bark of Taxus brevifolia analysis and isolation. J. Nat. Prod. 53 1249-1255. Wickremesinhe, E. R. M. and R. N. Arteca. 1998. Taxus species (yew) in vitro culture, and the production of taxol and other secondary metabolites. In Bajaj, Y. P. S. (ed.). Biotechnology in Agriculture and Forestry 41. Medicinal and Aromatic Plants X. Springer-Verlag. New York. p. 415-442. 

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]. 

Taxol (1), Fig (6), is another important diterpene with anticancer properties. It was isolated in 1971 from Taxus brevifolia Nutt. (Taxaceae), which is a slow growing shrub/tree, found in the forests of N.W Canada and USA. Taxol is one of over one hundred taxanes, which have been... 

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