Isolation, structure elucidation and approaches to the partial synthesis of new taxol analogs

Abstract

The western yew, Taxus brevifolia, was for many years the source of the important anticancer drug taxol, but it also contains many other natural taxoids. These compounds are of interest both from a structural viewpoint and also as a starting point for the synthesis of paclitaxel analogs. As a complement to our ongoing studies on the chemistry of paclitaxel and on its structure-reactivity relationships, we have investigated T. brevifolia extracts and have isolated two new taxoids. These are the A-nortaxol analog 7,13-deacetyl-9,10-debenzoyltaxchinin C 2.1 and 9-deacetyl-9-benzoyl-10-debenzoylbrevifoliol 2.4. The structures were elucidated by spectral methods, including extensive 2D nmr techniques. An approach to the synthesis of a novel A-nortaxol analog from one of the new compounds has been developed.