Taxoid synthesis

A. Fluorine-Containing Taxoids Synthesis and Biological Activity.92... 

In a taxoid synthesis, a cyclocarbonylation is performed with GDI at the 2- and 3-positions of the taxol ring system 925, prior to closure of the eight-memhered B ring, giving 926 in 95% yield [662]. 

A cydocarbonylation reaction akin to 246 — 247, forming 251 from 250, was accomplished with CDI in a taxoid synthesis by Nicolaou [187]. 

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

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... 

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]. 

Scheme 6 describes the taxoid library synthesis.28 The supported and highly functionalized intermediate 48 was produced from baccatin III 47 in several steps. These involved elaboration of baccatin III in solution by... 

These biological activities, combined with the use of these products as starting materials to prepare a- and p-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest [39—4-7], provide the motivation to explore new methodologies for the synthesis of substances based on the p-lactam core. 

With regard to the modification of the C-2 benzoate, several methods were reported for the introduction of other aryl or hetero-aromatic groups. However, those methods turned out to be not compatible to our purpose, which required modifications at C-2 as well as C-3. The successful routes to 2-modified baccatins 44 and 45 using 13-oxo-7-TES-DAB (41)72 are illustrated in Scheme 11.44 We also used 7-TES-(hexahydro)baccatin III (19) for the synthesis of 3 -modified 2-cyclo-hexanecarbonyl taxoids. 

In the course of our study on the rational design, synthesis and SAR of new antitumor taxoids, we became interested in incorporating fluorine(s) into paclitaxel and taxoids in order to investigate the effects of fluorine on cytotoxicity, blocking of known metabolic pathways, and its use as a probe for identifying bioactive conformation(s) of taxane antitumor agents. 

For the synthesis of a series of 3 -CF3-taxoids 71 and 72a-h, the ring-opening coupling of racemic iV-t-Boc-P-lactam 63 (excess) with 7-TES-baccatins 70,8, and... 

The transformation of three-membered oxiranes was successfully applied to the synthesis of thietane-containing taxoids, which were obtained in fair yield. 

Xiao X, Parandoosh Z, Nova MP, Design and synthesis of a taxoid library using radiofrequency encoded combinatorial chemistry, J. Org. Chem. 62 6029-6033, 1997. 

Metaferia et al. reported on the synthesis and cytotoxicity of C3 -C4 linked macrocyclic taxoids in 2001. The synthetic strategy was also based on RCM. Similar to Ojima et al. s finding, these compounds (100) are less active than paclitaxel in both cytotoxicity and tubulin assays.However, after careful inspection of the bioactive conformations of taxoids with computer simulation and nuclear magnetic resonance (NMR) experiments, they designed several C-4 and C3 -Ph orf/io-position linked taxoids (101) that were highly active, several times better than paclitaxel. ... 

Pulicanik, J.-R Bezard, D. Bourzat, J.-D. Bouchard, H. Zucco, M. Deprez, D. Commergon, A. Direct access to 2-debenzoyl taxoids by electrochemistry, synthesis of 2-modified docetaxel analogues. Tetrahedron Lett., 1994, 52 9717-9720. 

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