Synthesis and biological evaluation of C-13 amide-linked paclitaxel (Taxol) analogs

A new series of C-13 amido-containing paclitaxel analogs were accidentally synthesized during structure-activity relationship tests of paclitaxel (Taxol), an antitumor drug from Bristol-Myers Squibb. The analogs included 4-deacetyl-13-amidopaclitaxel, 13-amidopaclitaxel 4-(methyl carborate) derivatives, and 13-amidopaclitaxel. Biological profiling assays, in tubulin polymerization and in vitro cytoxicity assay against a human colon cancer cell line, determined the nonreactivity of the analogs.