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 wer e 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 ass ay. The inability of these homologs to induce microtubule formation ma y be due to unfavorable solution conformations, preventing productive interactions with the taxol binding site on microtubules.