Isolation, characterization and chemistry of taxanes from various taxus species

Paclitaxel is a potent anticancer agent isolated from the bark of the pacific yew (Taxus brevitfolia) tree. It is one of a class of compounds, the taxane diterpenoids, which are found in all species of yew. All species and varieties of yew are potential sources of paclitaxel or other taxanes that may serve as precursors to semi-synthetic paclitaxel. This work deals with an efficient means of isolating paclitaxel. It also deals with the isolation and identification of many novel taxanes.; Most published methods of isolating paclitaxel and other taxanes rely on chromatography on a polar stationary phase (i.e., silica, Florisil or alumina). Such media tend to permanently retain some amount of the materials run through them leading to loss of important compounds. In addition, re-use of the stationary phase is limited. A chromatographic medium which does not have these limitations was investigated.; Chromatography on reverse-phase C-18 bonded silica, at low pressure, provides an efficient means of isolating important taxanes (including paclitaxel) from extracts of yew bio-mass. The reverse-phase medium does not retain important compounds. It can also be washed (in-column) for re-use over numerous iterations thus providing some cost advantage for the more expensive medium.; Reverse-phase chromatography, in large scale, was applied to chloroform extract solids of Taxus brevifolia bark. It gave a yield of paclitaxel more than four times that in previously published works. Twice the yield of paclitaxel from Taxus x media Hicksii needles was also achieved via this method. Reverse-phase isolation proved to be an efficient means of isolating taxanes.; Additional isolation work was necessary to provide some compounds in pure form. Continued isolations were performed on these two plant sources to identify new compounds. Several novel taxanes are described. Other taxanes were isolated for the first time from these plant materials.; Little work has been published on the heartwood of Taxus brevifolia . The heartwood was also processed by large-scale reverse-phase chromatography to determine its taxane constituents. The wood contains many interesting and potentially useful taxanes including paclitaxel C, 10-deacetylpaclitaxel C and 10-deacetylpaclitaxel C-7-xyloside.