A NEW LARGE-SCALE PROCESS FOR TAXOL AND RELATED TAXANES FROM TAXUS-BREVIFOLIA

Purpose. In view of the demonstrated antitumor activity of taxol, read y availability of the drug is important. The current isolation methods starting from the bark of Taxus brevifolia involve multiple manipulat ions, leading to only taxol and in a yield of 0.01%. A new process con sisting of a single reverse phase column is introduced here, and the p resent purpose is to determine its large scale applicability. Methods. The chloroform extractable fraction of the bark of T. brevifolia is a pplied directly on to a C-18 bonded silica column in 25% acetonitrile/ water, with elution using a step gradient: 30-50% acetonitrile/water. On standing, eight different taxanes, including taxol, crystallize out directly from different fractions. The crystals are filtered and puri fied further by recrystallization. Taxol and four other taxanes are pu rified this way. The other three require a short silica column. Taxol is freed from cephalomannine by selective ozonolysis. Results. The lar ge scale process gave taxol (0.04%), 10-deacetylbaccatin III (0.02%), 10-deacetyl taxol-7-xyloside (0.1%), 10-deacetyl taxol-C-7-xyloside (0 .04%), 1O-deacetyl cephalomannine-7-xyloside (0.006%), taxol-7-xylosid e (0.008%), 10-deacetyl taxol (0.008%) and cephalomannine (0.004%). Pr ocessing of the needles of T. brevifolia gave brevifoliol (0.17%), and that of the wood, 10-deacetyl taxol-C-7-xyloside (0.01%) and 10-deace tyl taxol-C. Conclusions. The reverse phase column process is simpler (one column, direct crystallization), more efficient (eight taxanes ob tained simultaneously) and also gives higher yields.