Structure-activity studies of antitumor taxanes: synthesis of novel C-13 side chain homologated taxol and taxotere analogs.

Taxol and taxotere analogs with one carbon homologated side chains were synthesized from 10-deacetylbaccatin III and a key oxazolidineacetic acid intermediate, which was synthesized in four steps from (S)-(+)-2-phenylglycine. 10-Deacetyl-1a'-homotaxol and 1a'-homotaxotere were at least 27 times less active than taxol in the microtubule assembly assay. The inability of these homologs to induce microtubule formation may be due to unfavorable solution conformations, preventing productive interactions with the taxol binding site on microtubules.