- TAXANE AND ABEO-TAXANE ANALOGS
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The present application discloses new taxane analogs, intermediates and methods for producing them. The present application is also directed to pharmaceutical formulations comprising abeo-taxanes and methods of treating cancer with the abeo-taxanes.
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- An efficient synthesis of the taxane-derived anticancer agent ABT-271
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ABT-271, 1, has been identified as a promising anticancer agent. ABT-271 is a novel taxane possessing a C9-(R)-hydroxyl group as opposed to a C9-ketone which is present in Taxol and Taxotere. To further evaluate ABT-271 as a potential anticancer agent, an efficient synthesis was developed which allows the large scale synthesis of ABT-271. Ketalization of the 7,9-diol of 9-DHAB-III, 2, allows selective removal of the C13-acetate with phenyllithium. The resulting C13-hydroxyl group is then acylated using LiHMDS and β-lactam 22 to give ABT-271 in protected form. The protecting groups were removed first by acidic hydrolysis followed by basic hydrolysis to provide ABT-271. Application of this synthetic sequence provided over 600 g of ABT-271, 1.
- DeMattei,Leanna,Li,Nichols,Rasmussen,Morton
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p. 3330 - 3337
(2007/10/03)
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- Rearrangement of the major taxane from Taxus canadensis
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The rearrangement of 9-dihydro-13-acetylbaccatin III, the major taxane from Taxus canadensis, has been studied. Two new cyclization products as well as one novel degradation compound are reported. Their structures were determined by spectroscopic techniques.
- Zamir, Lolita O.,Cherestes, Alice D.,Nikolakakis, Anastasia,Sauriol, Francoise,Mamer, Orval
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p. 7917 - 7920
(2007/10/03)
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- Antitumor Activity of 9(R)-Dihydrotaxane Analogs
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A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated from Taxus canadensis.The selective C-13 deacetylation of this isolate has allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs.In general, this series
- Klein, Larry L.,Li, Leping,Maring, Clarence J.,Yeung, Clinton M.,Thomas, Sheela A.,et al.
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p. 1482 - 1492
(2007/10/02)
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- Synthesis of 9-Dihydrotaxol: A Novel Bioactive Taxane
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The synthesis of 9-dihydrotaxol (8) is described via a novel deacylation reaction.This analog exhibits increased activity in the microtubule assay. Key Words: Taxanes; deacylation; 9-dihydrotaxol; 9-dihydrobaccatin III; 7,9-acetonide.
- Klein, Larry L.
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p. 2047 - 2050
(2007/10/02)
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