CHEMICAL SYNTHESIS AND BIOLOGICAL EVALUATION OF C-2 TAXOIDS

An efficient, general method for the synthesis of 1,2-hydroxy esters b y regioselective nucleophilic opening of 1,2-cyclic carbonate systems has been developed. A reliable and practical route giving access to th e taxoid carbonate 2 from the readily available 10-deacetylbaccatin II I (13) has been established. Nucleophilic opening of the carbonate 2 w ith a variety of nucleophiles provided a number of novel C-2 Taxols. W ater-soluble taxoid onium salts (e.g., 31e, 31n, 32, and 34b) were als o synthesized and studied. A selected number of taxoids were subjected to cytotoxicity and tubulin polymerization assays as well as in vivo studies. The results of these studies are reported herein.