Taxoids

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

Total synthesis of taxoids, diterpenoids with 0-heterocyclic fragments 97H(46)727. 

Fallis A. G. From Tartrate to Taxoids a Donhle, Intramolecnlar Diels-Alder Strategy Pure Appl. Chem. 1997 6, 495-500... 

In this work, a suspension culture of Taxus chinensis, which produces a bioactive taxoid, taxuyunnanine C (Tc), was taken as a model plant cell system. Experiments on the timing of jasmonates addition and dose response indicated that day 7 and 100 pM was the optimal elicitation time and concentration for both cell growth and Tc accumulation [8]. ITie Tc accumulation was increased more in the presence of novel hydroxyl-containing jasmonates compared to that with methyl jasmonate (MJA) addition. For example, addition of 100 pM... 

For example, an alumina layer with a nonaqueons mobile phase was optimized for the separation of the taxoid fraction from ballast snbstances [5]. Figure 11.3 shows the densitogram obtained for Taxus baccata cmde extract chromatographed on the alnmina layer developed with nonaqueous elnents. The nse of ethyl acetate and dichloromethane enables elntion of nonpolar fractions (chlorophylls and waxes) and purification of the starting zone (Figure 11.3a). In this system, all taxoids are strongly retained on the alumina layer. The use of a more polar mobile phase... 

Taxoids Taxus baccata SiOj B - CHCI3 - MejCO - MeOH UV 254 Optimization of 4 C/)... 

Taxoids Taxus walichiana cell SiOj B + MejCO UV 254 nm Isolation 83... 

Systems with different selectivity were nsed for the separation of 10-deacetyl-baccatin III (10 DAB 111) from yew extracts [69]. A silica column with stepwise gradient elution with aqneous methanolic mobile phases can be nsed for separation of the taxoid fraction from nonpolar materials, partial separation of the taxoid fraction into a polar one (containing 10-DAB 111), and for a medinm polarity taxoid fraction (containing paclitaxel and cephalomannine). Most polar material (tannins... 

FIGURE 11.21 Densitograms of PLC of Taxus baccata fraction from preparative column (silica/aqueous methanol) containing unknown taxoid (Tax 1) introduced to the layer with a set of capillaries with simultaneous evaporation of solvent from the starting band. System silica/CH2Cl2 + DX + Me2CO + MeOH (84 10 5 1). Plates double developed (a) 0.3 ml of fraction introduced (b) 0.5 ml of fraction introduced (c) 1 ml of fraction introduced to the layer. 

Ketchum, R.E.B., Rithner, C.D., Qiu, D. et al. (2003) Taxus metabolomics methyl jasmonate preferentially induces production of taxoids oxygenated at C-13 in Taxus x media cell cultures. Plant Metabolomics, 62, 901-909. 

The same author used this strategy to synthesize tricydic taxoid skeletons 55, an intramolecular Diels-Alder approach that proceeds in the direction from left to right (ring A to BC) (Scheme 9.14) [56], Once again, microwave irradiation was necessary to perform the required cycloaddition in good yield. 

Finally a French group developed a novel taxoid photoprobe [111], which allowed the first identification of an amino-acid sequence in the a-subunit (281-304) together with expected labeling in the /1-subunit (217-229). 

Since the discovery of the high anticancer activity of taxol, much attention has been drawn to its asymmetric synthesis. The total synthesis stood for more than 20 years as a challenge for organic chemists. The compound taxoids are diterpenoids isolated from Taxus species and have a highly oxidized tricyclic carbon framework consisting of a central eight-membered and two peripheral six-membered rings (see Fig. 7-2).21... 

Novel macrocyclic and open-chain taxoid mimicking compounds were synthesized. Two of these, compounds 283 and 284, were found to possess cytotoxicity with micromolar level IC50 values against human breast cancer cell lines <2004BML3491>. 

The semisynthesis of taxol [1], as well as the synthesis of taxoid model systems have been the focus of extensive research efforts in many laboratories, all over the world, which have greatly simplified the total synthesis of taxol itself. An excellent review by Nicolaou et al. has recently been published in Angewandte Chemie [2]. 

The cyclic carbonate in compound 23 plays the role of a rigid auxiliary ring which facilitate the ring closure of the preorganised dialdehyde 23 by a McMurry type cyclisation [11] to afford the taxoid ABC ring system 24 in 23% yield, the... 

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... 

Paclitaxel (96) Diterpene taxoid Cabazitaxel Oncology Tubulin binding Phase III Sanofi-Aventis 658-662... 

Kingston DO Newman DJ. (2007) Taxoids Cancer-fighting compounds from nature. Curr Opin Drug Discovery Dev 10 130-144. 

Cistemino S, Bourasset F, Archimbaud Y, Semiond D, Sanderink G, Scherrmann JM. (2003) Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats. Br J Pharmacol 138 1367-1375. 

Kurata T, Shimada Y, Tamura T, Yamamoto N, Hyodo 1, Saeki T, Takashima S, Fujiwara K, Wakasugi H, Kashimura M. (2000) Phase 1 and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour intravenous infusion in patients with advanced solid tumors. J Clin Oncol 18 3164-3171. 

Sessa C, Cuvier C, Caldiera S, Bauer J, Van Den Bosch S, Monnerat C, Semiond D, Perard D, Lebecq A, Besenval M, Marty M. (2002) Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced sohd tumors. Ann Oncol 13 1140-1150. 

Ojima I, Slater JC, Kuduk SD, Takeuchi CS, Gimi RH, Sun CM, Park YH, Pera P, Veith JM, Bemacki RJ. (1997) Syntheses and structure-activity relationships of taxoids derived from 14 betahydroxy-lO-deacetylbaccatin III. 

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