Conformationally restricted macrocyclic analogues of paclitaxel were prepared, by connecting the 3'-phenyl group the 2-benzoate moiety with two-atom tethers to mimic the 'hydrophobic collapse' paclitaxel conformation. The analogues did not show activity in a tubulin assembly assay.
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Acknowledgments: These studies were supported by The National Cancer Institute. We would like to thank the Scientific Education Partnership of Hoechst Marion Roussel for postdoctoral fellowship support to TCB. The authors would also like to thank Drs. G. Grunewald, C.-H. Czaplinski, R. K. Jalluri and S. Victory for their help with molecular modeling.