Antitumor Activity of 9(R)-Dihydrotaxane Analogs

A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated from Taxus canadensis. The selective C-13 deacetylation of this isolate has allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs. In general, this series has shown greater stability and water solubility than the 9-carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity activities relative to taxol. Placement of polar functionalities at the C-7 position results in loss of activity whereas alkylation or acylation of either C-7 or C-9 hydroxyl groups ameliorate the activity.