- Conformation of Taxotere and analogues determined by NMR spectroscopy and molecular modeling studies
-
Taxol 1 and Taxotere 2 are antitumor compounds interacting with tubulin proteins. In order to find the best conformational fit to the receptor site, the structures of taxotere and twelve analogues showing various in vitro biological activity on tubulin, have been investigated by 1H NMR spectroscopy and molecular modeling studies. These structures were compared to that of Taxotere 2 obtained by X-ray analysis. The results obtained from these studies suggest that the most active 2′R,3′S compounds possess a conformation in which the benzoate group at C-2 holds the side chain in a defined position due to hydrophobic interactions between this group and the N-amido or N-carbonyloxy group at C-3′. This situation together with the presence of hydrogen bonding between 2′OH-3′NH and 2′OH-1′C - O gives rise to a specific orientation of the hydroxyl and phenyl groups at C-2′ and C-3′. On the other hand, the 2′S,3′R isomers which display low in vitro biological activity (ie: on tubulin), such as isotaxotere 8, possess a different conformation with no hydrophobic interactions between the side chain and the taxan skeleton.
- Dubois, Joelle,Guenard, Daniel,Gueritte-Voegelein, Francoise,Guedira, Nourredine,Potier, Pierre,Gillet, Brigitte,Beloeil, Jean-Claude
-
-
Read Online
- An efficient semi-synthetic method to construct docetaxel via sterically crowded linear side chain esterification
-
An efficient semi-synthetic method was developed to construct docetaxel 1 by using N,N-di-Boc protected linear isoserine derivative 5 as the side chain source, in which, bulky protecting group on the nitrogen atom blocked C-2′ position and prohibited unav
- Shen, Xin,Yang, Jidong,Zhan, Huaxing,Wang, Hu,Wu, Shaohong,Chen, Zili
-
-
- METHOD FOR PREPARING TAXANE DERIVATIVES
-
Provided is a method for preparing a taxane derivative, comprising: carrying out condensation of a phenylisoserine derivatives having a protective group introduced thereto or a mixture of isomers thereof, as a side chain, with a baccatin III derivative or 10-deacetyl-baccatin III derivative to obtain a mixture of isomers; separating the isomers via chromatography; and carrying out a reversion of the stereochemical structure of a selectively separated isomer, which is suitable for producing a taxane derivative in a large scale with high yield.
- -
-
Page/Page column 9
(2012/02/15)
-
- METHOD FOR PREPARING TAXANE DERIVATIVES
-
Provided is a method for preparing a taxane derivative, comprising: carrying out condensation of a phenylisoserine derivatives having a protective group introduced thereto or a mixture of isomers thereof, as a side chain, with a baccatin III derivative or 10-deacetyl-baccatin III derivative to obtain a mixture of isomers; separating the isomers via chromatography; and carrying out a selective reversion of the stereochemical structure of a separated isomer, which is suitable for producing a taxane derivative in a large scale with high yield.
- -
-
Page/Page column 17
(2010/11/05)
-
- PROCESS FOR THE PREPARATION OF DOCETAXEL, ITS INTERMEDIATES, AND METHODS FOR PREPARATION THEREOF
-
The present invention disclosed an process for preparing docetaxel 1, including the following steps: a) hydroxyl acylation reaction of compound 2 and 3 to obtain compound 4; b) deprotection group R1 of the hydroxyl group of compound 4 obtained
- -
-
Page/Page column 7
(2010/12/29)
-
- ONE POT SYNTHESIS OF TAXANE DERIVATIVES AND THEIR CONVERSION TO PACLITAXEL AND DOCETAXEL
-
A process is provided for the semi-synthesis of taxane intermediates useful in the preparation of paclitaxel and docetaxel, in particular, the semi-synthesis of protected taxane intermediate in a one pot reaction, of protecting the C-10 and attaching a si
- -
-
Page/Page column 33
(2010/11/30)
-