LARGE-SCALE PROCESS FOR HIGH PURITY TAXOL FROM BARK EXTRACT OF TAXUS YUNNANESIS

Abstract

A large-scale separation of taxol from semi-purified bark extract of Taxus yunnanesis was investigated. The chromatographic behavior of taxol and two close eluting analogues, cephalomannine and 7-epi-10-deacetyltaxol, was systematically studied on a C₁₈ bonded phase column with different mobile phases in reverse phase mode. According to the notably different selectivity of the methanol and acetonitrile with water in the mobile phase and the most important requirement of capacity in preparative chromatography, the optimum suitable mobile phase used in a large-scale isolation of taxol and 7-epi-10-deacetyltaxol on a preparative C₁₈ column was given. Cephalomannine was eliminated by ozonolysis and, then after, separated throughout a normal phase silica column. The whole large-scale process for high purity taxol from the bark extract from Taxus yunnanesis consisted of a preliminary purification with Biotage FLASH 150i system based on a prepacked normal phase silica cartridge, followed by using a C₁₈Nova-pak™ column in a Waters PrepLC™ 4000 preparative HPLC system.

ACKNOWLEDGMENTS

The authors are grateful to Prof. H-M. Wu and Dr. C-Y. Cao, of the Shanghai Institute of Organic Chemistry, for the use of the NMR facilities and mass spectral assistance.