A Large Scale Process for Paclitaxel and other Taxanes from the Needles of Taxus x Media Hicksii and Taxus Floridana Using Reverse Phase Column Chromatography

Abstract

Although the renewable, needle bio-mass of Taxus x media Hicksii was proposed as the future source for paclitaxel in 1990, no details for the actual isolation of paclitaxel and other taxanes have been published, other than testing the extracts by HPLC analysis. Compared to the bark, the needle source poses additional problems, eg. chlorophylls, waxes and co-eluting taxanes, and thus, there is a need for an efficient method.

We have developed a new large-scale process based on a single reverse phase column, which takes the CHCl₃ extract of T x media Hicksii directly, and is eluted with acetonitrile (30–60%) in water. Paclitaxel and five other taxanes crystallize out from the fractions, and they are filtered and recrystallized. The taxanes that co-elute with paclitaxel are removed by ozonolysis and a short silica column to give paclitaxel in a yield of 0.012–0.015 % from the dry needles.

The needle mass of T. floridana was also processed by the same method on a pilot-plant scale. From the fresh needles, paclitaxel (0.01%) and 10-deacetyl baccatin III (0.06%) and two other taxanes are obtained. A discussion on the two plants as sources for paclitaxel is presented.