Anastasia Nikolakakis

Semi-Synthesis of an O-Glycosylated Docetaxel Analogue

A 7beta-O-glycosylated docetaxel analogue was semi-synthesized from 9-dihydro-13-acetylbaccatin III, the most abundant taxane isolated from the needles of Taxus canadensis. It was shown to be more bioactive than paclitaxel according to the tubulin assay. It had a reduced potency in the MCF7 cell line cytotoxicity assay compared to paclitaxel, but it demonstrated better activity against the drug resistant cell line MCF7-ADR. In addition, the presence of one sugar moiety on C-7 doubled the water solubility versus that of paclitaxel.

Taxus canadensis Abundant Taxane: Conversion to Paclitaxel and Rearrangements

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.

Microbial and reducing agents catalyze the rearrangement of taxanes

5alpha, 7beta, 9alpha, 10beta, 13alpha-Pentahydroxy-4(20),11(12)-taxadiene derivative 1 was converted to two unprecedented 1(15-->11)abeo-taxanes and a taxane derivative with a C10-C11 double bond by Absidia coerula ATCC 10738a. A similar compound was obtained from treatment with zinc of a triacetoxy-4(20),11(12)-taxadiene derivative.

Acid catalyzed rearrangement and acyl migration studies on 9-dihydro-13-acetylbaccatin-III, a major taxane from Taxus canadensis

Abstract A detailed investigation of the rearrangement of the major taxane from Taxus canadensis enables to suggest the sequence of the reactions involved: 9-dihydro- 13-acetylbaccatin III → abeo-taxanes with intact oxetane and acyl migration → abeo-taxanes with intact oxetane and deacylation → abeo-taxanes with opening of the oxetane and various acyl migrations including two unusual benzoyl shifts.

Evidence for enzymatic formation of isoprephenate from isochorismate

Abstract Isoprephenate, a hypothetical intermediate in the biosynthesis of m -carboxy aromatic amino acids, has not been demonstrated in vitro or in vivo . Evidence for the enzymatic conversion of isochorismate to isoprephenate was obtained in crude extracts derived from Nicotiana silvestris .

Structures of new metabolites from Fusarium species : an apotrichothecene and oxygenated trichodienes

Abstract Three new natural products were isolated from Fusarium spp , one apotrichothecene and two oxygenated derivatives of trichodiene. The apotrichothecene was a precursor to apotrichodiol and sambucinol.

Design and syntheses of putative bioactive taxanes

Reduction of 5 alpha-hydroxy-7 beta,9 alpha,10 beta-triacetoxy-4(20), 11(12)-taxadien-13-one 1 with activated zinc in glacial acetic acid led to rearranged products, including compounds with double bonds at C3-C4, C10-C11 or with an epoxide at C11-C12. Molecular modeling studies suggested that addition of a side chain at C-20 or C-5 of the taxanes with a C3-C4 double bond might lead to bioactivity. Semi-syntheses and results of bioactivities are discussed.

Corrigendum to “Design and Syntheses of Putative Bioactive Taxanes” [Bioorg. Med. Chem. (2002) 2387–2395]

Anastasia Nikolakakis, Jian Hui Wu, Gerald Batist, Francoise Sauriol, Orval Mamer and Lolita O. Zamir* Human Health Research Center, INRS-Institut Armand-Frappier, Universite du Quebec, 531 Boulevard des Prairies, Laval, Quebec, Canada H7V 1B7 McGill Center for Translational Research in Cancer, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Suite D-127, Montreal, Quebec, Canada H3T 1E2 Department of Chemistry, Queen’s University, Kingston, Ontario, Canada K7L 3N6 Biomedical Mass Spectrometry Unit, McGill University, 1130 Pine Avenue west, Montreal, Quebec, Canada H3A 1A3