SYNTHESIS AND BIOLOGICAL-ACTIVITY OF A-NOR-PACLITAXEL ANALOGS

A number of paclitaxel analogues with a 5-membered A-ring (A-nor-pacli taxels, or (15 right-arrow 1)-abeo-paclitaxels) have been prepared in order to determine whether analogues of this class might have improved bioactivity as compared with paclitaxel. Most of the compounds synthe sized were less active than paclitaxel, but one analogue was equivalen t to paclitaxel in a tubulin-assembly assay, and another analogue was more cytotoxic than paclitaxel in two different cell lines of the NCI screen.