Selective synthesis of 14β-amino taxanes
- 作者：Arturo Battaglia ; Eleonora Baldelli ; Ezio Bombardelli ; Giacomo Carenzi ; Gabriele Fontana ; Maria Luisa Gelmi ; Andrea Guerrini and Donato Pocar
- 关键词：14β ; -Amino taxanes ; 10-DAB III ; Silyl enol ethers ; Electrophilic amination ; 13-Oxo-baccatins
- 刊名：Tetrahedron
- 出版年：2005
- 期刊代码：107_00404020
- 类别：ch
- 出版时间：2005
- 卷：61
- 期：32
- 页码：7727-7745
- 文件大小：705 K
摘要
The base induced deprotonation of H-14 of 7-triethylsilyl- (7-TES-) and 7-tert-butoxycarbonyl- (7-BOC-) protected 13-oxo-baccatins gave the corresponding enolates, which were selectively aminated with electrophilic nitrogen donors, such as azodicarboxylates and tosyl azide. In particular, tosyl azide gave the corresponding 7-BOC- and 7-TES-13-oxo-14β-azido-baccatin III. Alternatively, the last compound was prepared via NaN3 induced azidation of the 13-silyl enol ether of 7-TES-13-oxo-baccatin III under oxidative (cerium ammonium nitrate) conditions. The 13-silyl enol ether was obtained in a multistep process by DBU induced silylation of 7-TES-13-oxo-baccatin III. The 7-TES-13-oxo-14β-azido-baccatin III was used as a key intermediate for the synthesis of a new family of antitumour taxanes containing amino based functional groups at the C-14 position, such as: 14β-azido, 14β-amino, 14β-amino 1, 14-carbamate, 14β-amino 1, 14-thiocarbamate, and 14β-amino N-tert-butoxycarbonyl-1,14-carbamate.