Semisynthesis Process for the Preparation of 10-Deacytyl-N-Debenzoyl-Paclitaxel
AssigneeIndena S.p.A.
InventorsBruno Gabetta, Andrea Gambini, Ezio Bombardelli, Gabriele Fontana
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Abstract
The invention relates to a process for the preparation of 10-deacetyl-N-debenzoyl-paclitaxel, a synthon useful for the preparation of taxanes with antitumour activity, and intermediates for the preparation thereof. The invention also discloses a process for the preparation of Docetaxel starting from said compound of formula (I).
Claims16
A process for the preparation of 10-deacetyl-N-debenzoyl-paclitaxel (I)
- comprising the following steps:
- a) reaction of 2-(2,4-dimethoxyphenyl)-3-(2-nitrobenzenesulfenyl)-4(S)-phenyl-5(R)-oxazolidinecarboxylic acid (V)
- with 10-deacetyl-bis-7,10-trichloroacetylbaccatin III (VI)
- to give 2-(2,4-dimethoxyphenyl)-3-(2-nitrobenzensulfenyl)-4(S)-phenyl-5(R)-oxazolidine carboxylic acid, 10-deacetyl-7,10-bis-trichloroacetylbaccatin III 13-yl-ester (VII)
- b) hydrolysis of the trichloroacetyl groups at the 7- and 10-positions of the compound of formula (VII) to give 2-(2,4-dimethoxyphenyl)-3-(2-nitrobenzensulfenyl)-4(S)-phenyl-5(R)-oxazolidine carboxylic acid, 10-deacetylbaccatin III 13-yl-ester (VIII)
- c) acid treatment of the compound formula (VIII) to give 10-deacetyl-N-debenzoyl-paclitaxel (I).
2-(2,4-Dimethoxyphenyl)-3-(2-nitrobenzensulfenyl)-4(S)-phenyl-5(R)-oxazolidine carboxylic acid, 10-deacetyl-7,10-bis-trichloroacetylbaccatin III 13-yl-ester (VII)
2-(2,4-Dimethoxyphenyl)-3-(2-nitrobenzensulfenyl)-4(S)-phenyl-5(R)-oxazolidine carboxylic acid, 10-deacetylbaccatin III 13-yl-ester (VIII)
A process for the preparation of 10-deacetyl-bis-7,10-trichloroacetylbaccatin III with a content of the corresponding 7- or 10-mono-trichloroacetyl derivatives lower than 0.1% as determined by HPLC, comprising the silica gel chromatography of the reaction mixture.
A process for the preparation of docetaxel having a purity degree higher than 99% obtained without chromatographic purification and with a content of corresponding 7-epi or 10-dehydro derivatives lower than 0.1% each.
Docetaxel having a purity degree higher than 99% and with a content of corresponding 7-epi or 10-dehydro derivatives lower than 0.1% each.
Dependencies are inferred from the claim text.