SYNTHESIS AND BIOLOGICAL EVALUATION OF C-3'-MODIFIED ANALOGS OF 9(R)-DIHYDROTAXOL

Taxol (1) is considered a mast exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihyrdrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family, Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino group might be optimal. However, relatively little is known about the effects of the 3'-phenyl ring on activity. The synthesis and biological evaluation of analogs of 3 modified at the C-3' position are described. This study revealed that the 3'-phenyl ring was not required for activity and identified several compounds which had equal or greater in vitro and in vivo activity than taxol.