76446-91-8Relevant academic research and scientific papers
The taxol pathway 10-O-acetyltransferase shows regioselective promiscuity with the oxetane hydroxyl of 4-deacetyltaxanes
Ondari, Mark E.,Walker, Kevin D.
scheme or table, p. 17187 - 17194 (2009/04/13)
The 10-deacetylbaccatin III:10β-O-acetyltransferase isolated from Taxus cuspidata regiospecifically transfers short-chain alkanoyl groups from their corresponding CoA thioesters to the C10 hydroxyl of 10-deacetylbaccatin III. This 10-O-acetyltransferase along with five other Taxus acyltransferases on the paclitaxel (Taxol) biosynthetic pathway and one additional Taxus-derived acyltransferases of unknown function were screened for 4-O-acetyltransferase activity against 4-deacetylbaccatin III, 7-acetyl-, 13-acetyl-, and 7,13-diacetyl-4-deacetylbaccatin III. These 4-deacyl derivatives were semisynthesized from the natural product baccatin III via silyl protecting group manipulation, regioselective reductive ester cleavage with sodium bis(2-methoxyethoxy)aluminum hydride, and regioselective acetylation with acetic anhydride. Assays with the 4-deacetylated diterpene substrates and acetyl CoA revealed the taxane 10β-O-acetyltransferase was able to catalyze the 4-O-acetylation of 4-deacetylbaccatin III to baccatin III and 13-acetyl-4-deacetylbacatin III to 13-acetylbaccatin III, although each was converted at lesser efficiency than with the natural substrate. In contrast, this enzyme was unable to acetylate 7-acetyl-4-deacetylbaccatin III and 7,13-diacetyl-4-deacetylbaccatin III substrates at C4, suggesting that the C7 hydroxyl of baccatin III must remain deacylated for enzyme function. The biocatalytic transfer of an acyl group to the tertiary hydroxyl on the oxetane moiety at C4 of the taxane ring demonstrates that the regiochemistry of the 10β-acetyltransferase is mutable.
Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents
Ojima, Iwao,Borella, Christopher P.,Wu, Xinyuan,Bounaud, Pierre-Yves,Oderda, Cecilia Fumero,Sturm, Matthew,Miller, Michael L.,Chakravarty, Subrata,Chen, Jin,Huang, Qing,Pera, Paula,Brooks, Tracy A.,Baer, Maria R.,Bernacki, Ralph J.
, p. 2218 - 2228 (2007/10/03)
A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure - activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.
Taxus canadensis abundant taxane: Conversion to paclitaxel and rearrangements
Nikolakakis, Anastasia,Caron, Gaetan,Cherestes, Alice,Sauriol, Francoise,Mamer, Orval,Zamir, Lolita O.
, p. 1269 - 1280 (2007/10/03)
An efficient conversion of Taxus canadensis abundant taxane, 9-dihydro-13-acetylbaccatin III to baccatin III is described. Since the synthesis of paclitaxel from baccatin III has been reported, this work can be used for additional supply of this powerful anticancer drug. In addition, new taxanes derived from skeletal rearrangements originating from oxidation-reduction reactions of the Canadian yew major taxane, are reported. Copyright (C) 2000 Elsevier Science Ltd.
New taxanes as highly efficient reversal agents for multidrug resistance in cancer cells
Ojima, Iwao,Bounaud, Pierre-Yves,Takeuchi, Craig,Pera, Paula,Bernacki, Ralph J.
, p. 189 - 194 (2007/10/03)
New non-cytotoxic taxanes synthesized from 10-deacetylbaccatin III and special hydrophobic acylating agents show remarkable MDR reversal activity (≤99.8%) against drug-resistant human breast cancer cells when co-administered with paclitaxel or doxorubicin. This activity is ascribed to the highly efficient blocking of P-glycoprotein efflux by these new taxanes.
Anitleukemic Alkaloids from Taxus wallichiana Zucc.
Miller, Roger W.,Powell, Richard G.,Smith, Cecil R.
, p. 1469 - 1474 (2007/10/02)
A new antileukemic taxane alkaloid, cephalomannine (1a), has been isolated from leaves, stems, and roots of Taxus wallichiana Zucc.Cephalomannine is closely related to taxol (1b), a previously characterized antileukemic alkaloid, which also occurs in T. wallichiana but in lesser amounts than cephalomannine.The new alkaloid and its hydrolysis products were characterized by nuclear magnetic resonance, mass spetroscopy, and X-ray crystallography; taxol and two cytotoxic taxane congeners were also identified.
