C-3'-N-Acyl analogs of 9(R)-dihydrotaxol were synthesized from 7-ttietltylsilyl-9(R)dihydrobaccatin III and the corresponding (3R,4S)-N-acyl-3-(1-ethoxyethoxy)-4-phenylazetidin-2-ones. The analogs were tested in a microtubule assembly assay, and in an in vitro cytotoxicity assay. The highest activities observed were for the alkylcamamate substitutions.The isolation and characterization of 13-acetyl-9(R)-dihydrobaccatin III1 (1) offers the potential for a unique entry into the field of Taxol@ antitumor agents. This potential was actualized first with the synthesis of 9(R)-dihydrotaxol (2) which exhibimd in vitro activity comparable to that of Taxol@ (3).2 Therefore, having demonstrated that the 9(R)-hydroxyl group is a tolerated modification in the diterpenoid portion of the molecule, studies on the effects of side chain modifications on this new structure were intiated.The phenylisoserinate side chain at the C-13 position of Tax01 @ has been established as an essential component for in vitro cytotoxic activity by the promotion and stabilization of microtubule assembly. Studies involving systematic deletion and substitution analogs of the side chain have clearly established the natural regiochemical and stereochemical configuration (2'R,3'S) of the C-2' hydroxyl group and a C-3' acylated amine as being optimal.3 As a result, synthetic modifications have been focused on the C-3' nitrogen and on the C-3' phenyl group.4 Substitutions on and for the C-3' phenyl ring have been reported, and the full scope of modifications of this position and the consequences on in vitro activity are now beginning to be described5 Substitutions for the C-3' phenyl ring of the 9(R)-dihydrotaxol have been reported and will be the subject of another paper.6One of the more promising reported changes in the side chain of Taxol@ is the replacement of the 3'-Nbenzoyl group with a tert-butoxycarbonyl (t-BOC) group. A substantial increase in the tubulin activity and in vitro cytotoxicity was observed for Taxotere @, the 10_deacetyl-3'-N-t-BOC derivative of TaxolB.7 The structural divergence of the t-BOC group from the benzoyl group suggests a great potential for modification of this substituent of the side chain. Although one might infer from the clinical status of TaxotEre* that the t-BOC substitution represents an optimum substitution of the C-3' nitrogen in the Taxol@ series, the published data on the SAR leading to the t-BOC modification is fragmentary. We now report our results on the synthesis and SAR of some C-3'-N-acyl derivatives of 9(R)-dihydrotaxol