Synthesis and evaluation of some 10-mono- and 2',10-diesters of 10- deacetylpaclitaxel

Article abstract of DOI:10.1021/jm00017a026

10-Deacetylpaclitaxel, isolated from the bark of Taxus brevifolia, was converted into paclitaxel in one composite step (trimethylsilylation, acetylation, and desilylation) and in an overall yield of 80-85%. A series of 10-monoesters of 10-deacetylpaclitaxel are prepared by protection of the 2'- and 7-hydroxyls with a chloroacetyl group, acylation, and deprotection. Depending on the reaction conditions, the 10-monoesters, either exclusively or accompanied by the 2',10-diesters, are formed. The mono- and diesters were evaluated using the L-1210 cell culture assay. The 10-monoesters were comparable to paclitaxel and more active than the corresponding 2',10- diesters. The 10-[(4-methoxyphenyl)acetyl], 10-(2-nitrobenzoyl), and 10- (phenylacetyl) esters were found to be somewhat more active than paclitaxel.