New epothilone derivatives, used as mitosis regulators e.g. for treating malignant tumors, psoriasis or arthritis

摘要

Epothilone derivatives (I) are new. Epothilone derivatives of formula (I) (including stereoisomers and their mixtures) are new. R1a, R1b, R2a, R2b, R3, R4a, R4b = H, 1-10C alkyl, aryl or 7-20C aralkyl; or R1a + R1b or R2a + R2b or R4a + R4b = (CH2)n; n = 2-5; D'-E = CH2CH2, CH=CH, C?=C, oxirane-2,3-diyl, CH(OH)CH(OH) or CH(OH)CH2; R5 = 1-10C alkyl, aryl or 7-20C aralkyl; R6, R7 = H or together form an additional bond or O; R25 = H or 1-10C alkyl (optionally substituted by one or more of halo and/or OH); R8 = H; or 1-20C alkyl, aryl or 7-20C aralkyl (all optionally substituted); X = O, (OR9)2, 2-20C alkylene- alpha ,w-dioxy, (H, OR10) or CR11R12; R9 = 1-20C alkyl; R10 = H or protecting group; R11, R12 = H, 1-20C alkyl, aryl or 7-20C aralkyl; or CR11R12 = 5-7 membered carbocyclic ring; Y = O or H2; Z' = H or (H, OR13); R13 = H or protecting group. Independent claims are included for: (i) the preparation of (I); and (ii) novel intermediates of formulae (B), (C), (BC) and (ABC). R17 = OH, halo, protected hydroxy, PPh3<+>.halo<->, P(O)(OQ)2 or P(O)Ph2; Ph = phenyl; Q = 1-10C alkyl or Ph; R20 = H or protecting group; U = as for X; V, W = as X but not CR11R12; P' = protecting group.