Synthesis and evaluation of some 10-mono- and 2',10-diesters of 10-deacetylpaclitaxel.
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.
Rao
K V
KV
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Bhakuni
R S
RS
Johnson
J
J
Oruganti
R S
RS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004952:Esters; D007939:Leukemia L1210 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004952:Esters; D043823:Taxoids; C095360:10-deacetylpaclitaxel; D017239:Paclitaxel