从天然植物中提取紫杉醇原料的工艺.doc

Patent No. U.S. 6,759,539Assignee: Chaichem Pharmaceuticals International, Laval, Canada Title or Subject: Process for Isolation and Purification of Paclitaxel from Natural Sources This is the first of three patents covering paclitaxel 10a that is a naturally occurring compound found in the bark of yew trees and has been shown to be useful in treating various cancer tumours. The amount of 10a obtained from the bark is low, and hence, large amounts of biomass and solvents are needed to obtain reasonable quantities. Synthetic procedures are under investigation. This patent, covering 10a and its derivatives, describes an improved process to extract 10a from twigs and needles of coniferous trees of the genus Taxus. An earlier process from the same company to extract 10a involves several chromatography stages and recrystallisations, and it is not particularly amenable to large-scale production. The new procedure involves an initial aqueous extraction step to remove soluble impurities from the biomass. This is then followed by extraction of 10a with methanol, followed by its isolation by chromatography and crystallisation. The various stages of the process are summarised below: A porous bag containing twigs and needles of the tree is immersed in distilled water for 3 h at room temperature, the water is drained from the bag of biomass, and MeOH is added to the biomass in the tank at room temperature, the extract is collected and the solution concentrated by distilling off the MeOH, the crude solid is precipitated by addition of aqueous NaCl solution, collected by filtration, and then dried, the solid is dissolved in Me2CO, leaving resins and pigments, hexane is added to the solution to produce an oil that is collected and purified by low-pressure column chromatography at least once, the purified oil is dissolved in acetone and cooled to give crystals of 10a, and these may be recrystallised to improve the purity. -----------------------------------