ANTITUMOR-ACTIVITY OF 9(R)-DIHYDROTAXANE ANALOGS

A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has bee n 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 stab ility and water solubility than the 9-carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity activities relative to tax ol. 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.