Taxane Analogues Research Articles

ChemInform Abstract: Synthesis of Ring B‐Rearranged Taxane Analogues.

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Taxane analogues to be a main topic

Taxane analogues to be a main topic

An Efficient Approach toward Taxane Analogs: Atrop- and Diastereoselective Eight-Membered B Ring Cyclizations for Synthesis of Aromatic C-Ring Taxinine Derivatives

We have developed efficient methods for construction of the C-2 oxygenated aromatic C-ring taxane skeleton based on an eight-membered ring cyclization involving a Lewis acid-mediated intramolecular coupling reaction of the dienol silyl ether at C-10 and the acetal at C-9. The C-2 stereogenic center strongly influences the conformation of the forming eight-membered ring during the cyclization reaction. 1β,2α-Siloxy derivative 13b gives exo isomer 15 as the major product, and 1β,2β-silo derivative 13a exclusively yields endo isomer 14. Both of these cyclization products, which had undesired stereochemistry, were converted to stereochemically refined aromatic C-ring taxinine analogs by multistep transformations. The chelation-controlled, eigh-membered ring cyclisation of 1β,2α-hydroxy derivative 31 was found to give exclusively the desired 1β,2α,9α,10β-endo isomer 16 in good yield. This remarkably stereoselective cyclisation, when combined with stereocontrolled AC ring coupling reactions, should provide an efficient, convergent route toward various taxane derivatives. The aromatic C-ring taxinine analogs could be converted to natural taxinine by further transformation of the aromatic C-ring

Synthesis of Ring B-Rearranged Taxane Analogs

Reaction of the C-7 hydroryl group on the 9-dihydrotaxane skeleton with triflic anhydride causes a major skeletal rearrangement to occur leading to contraction of ring B. In addition the formation of a ring C-fused cyclopropane structure occurs. The requisite C-13 phenylisoserinate side chins are appended via an initial deacylation of the C-13 acetate followed by reacylation and deprotection. These rearranged compounds show very similar structural features with the parent 9-dihydrotaxane skeleton and also retain biological activity

A concise synthesis of a highly functionalized C-aryl taxol analog by an intramolecular Heck olefination reaction

A palladium(0) catalyzed intramolecular Heck olefination used to establish the C 10C 11 connection in a highly functionalized taxane analog is described.

Analysis of taxol and related taxanes from taxus canadensis using liquid chromatography combined with mass spectrometry or tandem mass spectrometry

AbstractA liquid chromatography/mass spectrormetry (LC/MS) method using nebulizer‐assisted electrospray (ionspray) is described for the analysis of taxol and related taxane analogs in plant extracts from Taxus canadensis. The method used a reverse‐phase liquid chromatography gradient elution which was entirely compatible with the operation of ionspray ionization. Abundant protonated molecules with limited fragmentation were obtained using this ionization technique, and provided adequate sensitivity for monitoring taxol in crude resin extracts. The LC/MS method was evaluated for the analysis of taxol present at levels of 0.2% in resin extracts. Using selected‐ion monitoring, the method provided detection limits of 50 ng/mL. In addition, other taxane analogs were identified in crude resin extracts using liquid chromatography combined with tandem mass spectrometry. Parent‐ion scans for a fragment ion characteristic of the taxane nucleus provided the necessary selectivity and sensitivity for the identification of potentially active diterpenes in complex extracts.

Taxol: the first of the taxanes, an important new class of antitumor agents.

The taxanes represent the first class of antimicrotubule agents with a new mechanism of cytotoxic action since the introduction of the vinca alkaloids several decades ago. These compounds may prove to be the "anticancer drugs of the 1990s," just as the anthracyclines and the platinum compounds were the "anticancer drugs" of the 1970s and 1980s. Like the platinums, taxol, the prototypic taxane, has shown significant antineoplastic activity in patients with advanced ovarian cancer, with response rates ranging from 20% to 50%. Moreover, taxol has been shown to be useful in patients with platinum-resistant ovarian cancer. Although phase II screening is not yet complete, the results of phase II studies of taxol in advanced cancers of the ovary, breast (response rates, 56% to 62%), and lung (response rates, 21% to 24%) have rekindled interest in the microtubule as a prime strategic target for cancer therapy. After briefly reviewing the mechanisms of antineoplastic action and resistance and the results of preliminary clinical and pharmacological studies, this review will discuss several critical issues that will be addressed in future clinical trials, developmental directions, and drug supply. Although this review will focus primarily on taxol, the results of preliminary investigations with the semisynthetic taxane analog taxotere will also be discussed.