Dichloromethane → Paclitaxel

Beteiligte Stoffe

Reaktionsschritte

In a further embodiment of this invention, the material obtained from the acetone/water precipitation comprising at least 40% paclitaxel is further purified by conventional silica chromatography using a methylene chloride/ethylacetate elution solvent system similar to a system described in U.S. Pat. Nos. 5,618,538 and 5,480,639 to ElSohly et al. The distinctive features of the second silica chromatography step of the present invention pertain to the feed material and to the scale of operation. The feed material for the second silica chromatography column of the present invention is a large scale preparation comprising at least 40% paclitaxel obtained from the acetone/water precipitation step and typically containing 1.5-2.0 kg of solids. This material is dissolved in 5-7 L of methylene chloride and applied to a 12-in×10-ft silica gel column packed in a stainless steel pipe. Preferably a layer of Celite is added to the top of the column to prefilter the feed material. The column is eluted with a mobile phase comprising a gradient of methylene chloride to 50% methylene chloride/ethyl acetate, and fractions are collected. Fractions are pooled to obtain a heart cut with at least 65% paclitaxel and less than 1% cephalomannine with typical yields of 92%-95% of the paclitaxel present in the feed material.

Herkunft & Nachweise