2 -0- taxol

Taxol is a registered trade name of Bristol-Myers Squibb. The generic name is paclitaxel. 

Suffness, ed., Taxol Science and Applications, CRC Press, Boca Raton, Florida, 1995. 

Another epoxidation followed by fragmentation, gives the bicyclic intermediate which contains the eight-membered ring and bridgehead double bond properly positioned for conversion to Taxol. 

The next phase of the synthesis is construction of the C ring. An aldol addition was used to introduce a pentenyl group at C-8, and the product was trapped as a carbonate between the C-2 and C-7 oxygens. The Davis oxaziridine was then used to introduce an oxygen at C-2. After reduction of the C-3 oxygen, a carbonate is formed, and C-2 is converted to a 

After oxidation of the vinyl group, the C ring is constructed by a Dieckmann cyclization. The resulting jS-keto ester is subjected to nucleophilic decarboxylation by phenylthiolate [step F (4-6)]. 

The mode of action of taxol involves binding to polymerized p-tubulin at a specific hydrophobic recepfor sife located deep within the tubular lumen. At standard therapeutic doses, which should lead to intracellular concentrations of 1-20 pM, taxol-tubulin binding promotes a stable tubulin conformation which renders the microtubules resistant to depolymerization and prone to polymerization. This promotes the elongation phase of microtubule dynamic instability at the expense of the shortening phase and inhibits the disassembly of the tubule into the mitotic spindle. In turn, this interrupts the normal process of cell division. At these 

FOUR-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

The biosynthetic pathway to taxol is considered to involve 19 steps from primary plant metabolism, and only a small number of the 400 taxoid metabolites are relevant taxol intermediates [239]. Many others represent the consequences of promiscuous oxygenase and AT activities. Thus, any approach aimed at increasing the production yields of taxol and its immediate precursors must take into account these numerous and apparently diversionary taxoid biosynthetic side routes leading to the production of taxoids different from taxol. 

The mid-section of the biosynthetic pathway to taxol involves the introduction of several oxygen functionalities to the taxane core. To study all subsequent biochemical 

Early work on taxanes has shown that there are several natural taxanes in which the structures analogous to the taxol C-13 side chain are esterified to 

The assembly of the isoprenoid moiety from a three-carbon fragment and a two-carbon fragment from glucose is reminiscent of the alternative isoprenoid pathway reported by Rohmer and co-workers (1993) in the 

The genes encoding several of the hydroxylation and acylation steps have been cloned and functionally expressed in E. coli (for a summary, see Marasco and Schmidt-Dannert, 2007). Whereas it was possible to produce the main skeleton, taxadiene, in recombinant bacteria and yeast in good yield, the later steps of taxol biosynthesis appear to be more difficult to achieve in recombinant systems at present (Jennewein et al., 2005 Dejong et al. 2006). 

In 1993, Stierle et al. (1993) had isolated Taxomyces andreanae, an endophytic fungus of Pacific yew, and could show that it was able to produce taxol (for a discussion, see Chapter 7). 

Betalains have received much attention from the food industry as natural colour additives (Adams et at, 1976 Pourrat et at, 1983). The betacyanins from red beet are used for colouring ice cream, jam and fruit conserves. Earlier interest in betacyanins came from their use in colouring red wine, although this was prohibited by law in 1892 due to the use of the apparently harmful pokeberry Phytolacca americana, extract (Dreiding, 1961). 

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Tautomerism Tax gallon Taxifolin Taxilan Tax incentives Taxol [330d9-d2-4]... 

Many notable examples of the synthesis of complex natural products from optically pure starting materials have been reported (70). One synthesis of considerable interest is that of taxol [33069-62-4] (74), a potent antitumor agent used clinically. The starting material (73) used ia the first total synthesis of taxol is produced ia enantiomericaHy pure form from inexpensive and readily available /-camphor [464-48-2] (72) (73). 

One method of synthesis of taxol analogues starts with a-pinene (8), the readily available and inexpensive monoterpene derived from the processing of turpentine from the pine tree (200). The a-pinene is oxidized to verbenone, which is then alkylated and converted to taxol analogues in a multistep process. 

Another monoterpene used as a starting material for taxol analogues is camphor (43), which is readily available naturally or can be produced synthetically (201,202). Total synthesis of taxol analogues may be the answer toward finding new compounds for the treatment of many types of cancer. 

Vinorelbine) taxol [33069-62 ] C47H51NO14 853.92 (52) nonsmaH cell lung cancer investigational dmg alopecia neutropenia ... 

In addition to the Vinca alkaloids and taxol, a limited number of other cytotoxic agents have been demonstrated to act at the level of tubulin. This... 

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 remarkable success of taxol in treatment of breast and ovarian cancers stimulated research efforts to synthesize taxol directly and to identify new antimitotic agents that, like taxol, stimulate microtubule polymerization. 

The. structure.s of vinbla.stine, vincri.stine, colchicine, and taxol. 

H2O2, NaHC03, THF. The 10-acetate, which is an a-keto acetate, is cleaved in the presence of the taxol side chain that is prone to hydrolysis with other reagents. ... 

Ethanolamine, IPA, reflux, 21 h, >50% yield. These conditions did not affect the C-10 acetate or the C-13 side chain of a taxol derivative. ... 

Three different silylene derivatives were used to achieve selective protection of a rnore hindered diol during a taxol synthesis. Treatment of the silylene with MeLi opens the ring to afford the more hindered silyl ether. 

The asymmetric epoxidation of electron-poor cinnamate ester derivatives was highlighted by Jacobsen in the synthesis of the Taxol side-chain. Asymmetric epoxidation of ethyl cinnamate provided the desired epoxide in 96% ee and in 56% yield. Epoxide ring opening with ammonia followed by saponification and protection provided the Taxol side-chain 46 (Scheme 1.4.12). 

Chemistry of taxol, anticancer diterpenoid with oxethane cycle as a part of fused system 98PAC331. 

Terpenoids with heterocyclic fragments as bioactive taxoids from Japanese yew Taxsus cuspidata and taxol biosynthesis 98H(47) 1111. 

Since the syntheses of urea and acetic acid in 1828 and 1845, respectively, synthetic chemists have come a long way in terms of the complexity of the target molecules they can reach. Progress was at first steady, but became rather dramatic in the second half of the 20th century. Vitamin Bi2, ginkgolide B, calicheamicin yi1, taxol, palytoxin, and brevetoxin B (Figure 3) are arguably six of the most impressive molecules to be synthesized to date. 

Taxol s journey to the clinic was slow and arduous. Initial difficulties with aqueous solubility and lack of knowledge regarding its mechanism, of action delayed its development until 1979 when, in another seminal paper in the field, S.B.Horwitz and her collaborators disclosed their findings on the interaction of taxol with microtubules.4 Taxol s unique biological action, which includes promotion of microtubule formation and microtubule stabilization, stimulated a renewed interest in taxol as a potential drug candidate. The problem of procuring adequate supplies of taxol became even... 

Not surprisingly, taxol has motivated the development of many synthetic strategies, and much fascinating science has emerged from research in this area.2,10 Attracted by the formidable challenge... 

Scheme 1. Strategic bond disconnections and retrosynthetic analysis of taxol (1).

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