Selective synthesis of 14β-amino taxanes

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.