STRUCTURE-ACTIVITY-RELATIONSHIPS OF TAXOL(R) - SYNTHESIS AND BIOLOGICAL EVALUATION OF C2 TAXOL ANALOGS

Red-Al was used to selectively remove the C-2 benzoate of 7,13-bisTES baccatin (8). Derivatization of the resulting C-2 hydroxy compound pro vided the corresponding p-nitrophenyl carbamate, the p-methoxy and p-n itrobenzoates, and cyclohexyl ester. Attachment of the taxol side chai n to the above four analogs via lactam (15) followed by desilylation p rovided five analogs of taxol modified at the C-2 position, including a C-1,C-2 cyclic carbonate. These five analogs were less potent than t axol in a tubulin polymerization assay and a cytotoxicity assay agains t human colon cancer cell line.