Lolita O. Zamir

Taxanes isolated from Taxus canadensis

Eight taxanes isolated from Taxus canadensis have been rigorously characterized by spectroscopic techniques. Their relative amounts differ from other Taxus species. Three of these metabolites had not been reported in other Taxus species.

Taxoids from the needles of the Canadian yew.

Systematic characterization of the taxoids in the needles of Taxus canadensis led to the discovery of seven taxanes along with three known congeners. Their structures were rigorously established by spectroscopic methods as 15-benzoyl-10-deacetyl-2-debenzoyl-10-dehydro-abeo-baccat in III; 15-benzoyl-2-debenzoyl-7, 9-dideacetyl-abeo-baccatin VI; N-acetyl-N-debenzoyltaxol; 7,9,13-trideacetylbaccatin VI; 10-deacetyl-10-glycolylbaccatin IV; 1 beta-hydroxy-10-deacetyl-10-glycolylbaccatin I; and 7-deacetyltaxuspine L. These taxanes, specific to the Canadian yew, were co-isolated with taxacustin, taxagifine and 2-deacetyl-7,10-diacetyl-5-deaminoacyl taxine A previously found in Taxus cuspidata, baccata, and yunnanensis, respectively.

Novel taxanes from the needles of Taxus canadensis

Abstract Nineteen taxanes were characterized for the first time in the needles of the Canadian yew. Four of these metabolites are novel: taxinine-11, 12-oxide (1), 7-acetoxytaxuspine C (2), 5-cinnamoyltaxin B (3), and 7, 9-deacetyltaxinine B (4). Compound 1 is the second 11,12-epoxy-taxane known and 7-oxygenated-3, 11-cyclotaxane structures are unique to Taxus canadensis. In addition, taxinine and taxinine E were found to be major taxanes in the Canadian yew. The structures of all the taxanes were rigorously established by spectroscopic methods.

5-epi-Canadensene and other novel metabolites of Taxus canadensis

Abstract The Canadian yew distinguishes itself from other yews by the nature of its taxane metabolites. We are now reporting a new canadensene taxane whose stereochemistry is rigorously established. The three-dimensional structures of canadensene, 5-epi-canadensene and three other related bicyclic taxanes isolated from other yews were calculated using distance constraints derived from NMR data. The stereochemistry of the substituents, the polar acetate groups and the double bonds determine the 3D models. In addition, three new taxanes were also characterized and some biosynthetic speculations are presented.

Biosynthesis of 3-Acetyldeoxynivalenol and Sambucinol IDENTIFICATION OF THE TWO OXYGENATION STEPS AFTER TRICHODIENE

The first two oxygenation steps post-trichodiene in the biosyntheses of the trichothecenes 3-acetyldeoxynivalenol and sambucinol were investigated. The plausible intermediates 2-hydroxytrichodiene (2α- and 2β-) and 12,13-epoxytrichodiene and the dioxygenated compounds 12,13-epoxy-9,10-trichoene-2-ol (2α- and 2β-) were prepared specifically labeled with stable isotopes. They were then fed separately and/or together to Fusarium culmorum cultures, and the derived trichothecenes were isolated, purified, and analyzed. The stable isotopes enable easy localization of the labels in the products by 2H NMR, 13C NMR, and mass spectrometry. We found that 2α-hydroxytrichodiene is the first oxygenated step in the biosynthesis of both 3-acetyldeoxynivalenol and sambucinol. The stereoisomer 2β-hydroxytrichodiene and 12,13-epoxytrichodiene are not biosynthetic intermediates and have not been isolated as metabolites. We also demonstrated that the dioxygenated 12,13-epoxy-9,10-trichoene-2α-ol is a biosynthetic precursor to trichothecenes as had been suggested in a preliminary work. Its stereoisomer was not found in the pathway. A further confirmation of our results was the isolation of both oxygenated trichodiene derivatives 2α-hydroxytrichodiene and 12,13-epoxy-9,10-trichoene-2α-ol as natural metabolites in F. culmorum cultures.

Biosynthesis of the trichothecene 3-acetyldeoxynivalenol: cell-free hydroxylations of isotrichodermin.

3-Acetyldeoxynivalenol is the major trichothecene produced by the fungus Fusarium culmorum. Studies in vivo with F. culmorum have established the following biosynthetic precursors of 3-acetyldeoxynivalenol: isotrichoolu2002→u2002isotrichodiolu2002→u2002isotrichoderminu2002→u200215-deacetylcalonectrin, 7α-hydroxyisotrichodermin, 8α-hydroxyisotrichoderminu2002→u2002calonectrinu2002→u2002deoxynivalenol. In this paper, we describe in vitro investigations of one of these metabolic steps. The cell-free system of F. culmorum that converts isotrichodermin into 15-deacetylcalonectrin, 7α-hydroxyisotrichodermin, and 8α-hydroxyisotrichodermin is described here. This preparation requires NADPH but not NADH for activity and is not inhibited by carbon monoxide, cyanide, or known oxygenase inhibitors, such as SKF-525-A or ancymidol.Key words: trichothecene, Fusarium culmorum, cell-free system, isotrichodermin, 15-deacetylcalonectrin.

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.

New route to (3RS) (5R) (5-2H)- and (3RS) (5S) (5-2H)-mevalonolactones

Abstract The synthesis of mevalonolactone stereospecifically labeled at carbon 5 is described combining chemical reactions with an enzymatic reduction step.

Methyl 4-Carbomethoxy-3-Hydroxy-5-Methyl-Phenyl-Acetoacetate from the Disilylated Dianion of Methyl Acetoacetate

Abstract Recently, Chaley and Chan1 reported a novel synthesis of methyl olivetolate (3a) from the annelation of 1,3-bis(trimethylsiloxy)-1-methoxybuta-1,3-diene (1) with the acid chloride 2a and titanium tetrachloride at room temperature. In view of their success, we attempted to apply this methodology for a convenient synthesis of isotopically labelled orsellinic acid in order to unravel its biosynthesis to cyclopentanoids.