Isolation and characterization of taxanes and other compounds from various species of Taxus

Taxol is a promising antineoplastic agent originally reported in 1971 by Wani and Wall, isolated from the bark of the Pacific yew (Taxus brevifolia). Intensive research in the last decade has demonstrated that this drug possesses exceptional activity in the treatment of many difficult types of cancer.; From the beginning taxol has proven to be a difficult compound to obtain, with very low yields and a highly complex structure with many chiral centers and sensitive moieties. Originally obtained from the bark of a very slow growing tree, the possibility of growing various Taxus (yew) species under hydroponic conditions has been investigated in this project.; One local variety, known as Taxus floridana (Florida yew) was found to grow well and produce taxol and other useful taxanes. During initial investigations a simple and elegant method for the isolation of taxol using reverse phase bonded silica was developed. Generous funding by the University of Florida Division of Sponsored Research made possible the construction of a pilot plant scale facility where these isolation methods were successfully implemented.; Excellent yields and the isolation of many related taxanes have proven that this method is superior to currently approved processes used in the production of taxol. The failure of other researchers to employ bonded silica gel for preparative columns in the past may reflect experiences with analytical columns, but this method has proven to be quite exceptional and should be employed extensively.; This dissertation covers many crystalline and non-crystalline compounds isolated and characterized as a result of this project. Some results from the application of this technique for the isolation of taxanes from the needles of Taxus brevifolia, Taxus x media cultivar Hicksii, and T. floridana are presented. Similar experiments on the bark and wood of T. brevifolia are also described.