| 摘要 |
Preparation of a polyanion intermediate (I) for cyclosporin derivatives comprising treating a cyclosporin with an alkaline amide in liquid ammonia or a low molecular weight amine, in the presence of a co-solvent, is new. Independent claims are also included for: (a) the use of (I) in the preparation of cyclosporin derivatives of formula (IV) comprising adding an electrophile to (I), the functional groups of the cyclosporin being optionally protected, followed by deprotection if necessary and separation and purification; and (b) use of (I) in the preparation of 3-substituted cyclosporin derivatives comprising preparing (I) as above, followed by adding an electrophile to (I), optionally protecting the cyclosporin hydroxy groups, followed by deprotection if necessary, and separation and purification. R1 - R11 and Z1, Z2 and Z4-Z11 = e.g. as in cyclosporin A; R3 = e.g. -S-Alk-R0; Alk = 2-6C alkylene or 3-6C cycloalkylene; R0 = e.g. carboxy or alkoxycarbonyl. The full definitions are given in the 'Definition' section. |
