Abstract
Over 200 derivatives have been obtained through chemo-enzymatic transformation of the taxanes derived from cell cultures of Taxus chinensis. The reversal activity towards MDR tumor cells and cyto-toxicity of most these compounds were evaluated, and several derivatives exhibited powerful MDR reversal activity. The substrate-specificities of the two most important biotransformation reactions-C-7beta and 9alpha hydroxylations, were investigated and preliminarily concluded. In addition, some key intermediates in hypothetically biosynthetic pathway of taxoid were obtained. These results indicate that biotransformation combined with chemical transformation is a powerful approach to structural diversification of natural products, lead compound discovery and the study on the structure activity relationships of the derivatives. Moreover, biotransformation may mimic some steps in biosynthetic pathway of natural products and provide useful hints as to their biogenetic study.
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