Showing papers by "Daniel Guenard published in 1995"
TL;DR: Six novel docetaxel analogues that possess a N-(7-nitrobenz-2-oxa-1,3-diazo-4-yl)amido-6-caproyl chain in position 7 or 3' have been synthesized, demonstrating that the microtubule cytoskeleton constitutes their main subcellular localization.
41 citations
TL;DR: Zinc-promoted reduction of 13-oxobaccatin III derivatives leads to 11,12-dihydro analogs as mentioned in this paper, which are unstable and a skeleton rearrangement occurs leading to the cleavage of the C-10, C-11 bond.
11 citations
TL;DR: Hydroxylation is pharmacologically important, since hydroxylated compounds are the major metabolites of paclitaxel and docetaxel, leading in all cases to less cytotoxic derivatives which are readily eliminated.
Abstract: Publisher Summary This chapter presents metabolism and pharmacology of taxoids. Three main modifications occur in taxoids when they are introduced in the organism—namely, (1) epimerization, (2) hydrolysis, and (3) hydroxylation. After 72 h of incubation, the ratio of 7-epi-paclitaxel to paclitaxel varies from 0.36 to 0.48 in the cell and from 0.25 to 0.32 in the medium, depending on the cell line and on the initial concentration of paclitaxel. The epimerization of paclitaxel occurs in the medium in the presence or absence of cells. The reversible epimerization of the hydroxyl group at C-7 occurs with both paclitaxel and docetaxel. Two derivatives resulting from the hydrolysis of paclitaxel have been observed in human patients. Cleavage of the side chain at C-13 of the taxane ring results in the formation of baccatin III, while 10-deacetyl paclitaxel results from the cleavage of the acetyl group at the C-10 of the taxane ring. Hydroxylation is pharmacologically important, since hydroxylated compounds are the major metabolites of paclitaxel and docetaxel, leading in all cases to less cytotoxic derivatives which are readily eliminated.
5 citations
TL;DR: The title compound was obtained from 10-deacetylbaccatin III by the reduction of the C11=C12 double bond of the 13-keto derivative as mentioned in this paper.
Abstract: The title compound (systematic name: 8,9,10,11,12,12a,12b-tetradecahydro-6,9,11-trihydroxy-4a,8,13,13-etramethyl-4-triethylsiloxy-7,11-methano-1H -cyclodeca[3,4]benz[1,2b]oxete-12,12b-diyl 12b-acetate 12-benzoate), C 35 H 52 O 10 Si, was obtained from 10-deacetylbaccatin III by the reduction of the C11=C12 double bond of the 13-keto derivative. The saturation of the C11=C12 bond results in a large change in the orientation of the C13-OH hydroxy group. The distance between this group and the C4 acetyl group decreases leading to a strong hindrance of the hydroxy group, which explains the non-esterification at this position.
2 citations