The semisynthesis of the four novel taxol analogues baccatin III 13-(N-benzoyl-(2'R,3'S)-3'-(p-tolyl)isoserinate) (2), baccatin III 13-(N-p-toluoyl)-(2'R,3'S)-3'-phenylisoserinate) (3), baccatin III 13-(N-benzoyl-(2'R,3'S)-3'(p-trifluoromethylphenyl)isoserinate (4), and baccatin III 13-(N-p-trifluoromethylbenzoyl)-(2'R,3'S)-3'-phenylisoserinate) (5) from 7-triethylsilyl baccatin III (6) and the N-acyl-3-ethoxyethyl-4-aryl-2-azatidinones (11-14) is described. Derivatives 2, 3, and 5 demonstrated activity comparable to taxol (1) in the microtubule assembly assay and cytotoxicity against B16 melanoma cells. Derivative 4, however, was found to be an unstable product.
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Acknowledgments: We gratefully acknowledgef inancial assistancef rom the National Instituteso f Health (CA 52790), the American Cancer Society (IN-llSK), and the Biomedical Research Grant (RR 5606). Z. S. Cheruvallatha nd M. R. Mejillano were supportedb y the Wesley Foundation,W ichita, Kansas. A mixtureo f taxol and cephalomanninew as provided to us for theses tudiesb y the NationalC ancerI nstitute. We would like to thank Ms. Jeanne Ellermeier for her excellentt echnicala ssistance.