| 摘要 |
Production of a C16,C17-modified epothilone (IA) comprises subjecting a C3,C7-optionally protected epothilone A or B (IIA) to: (a) hydrogenation of the 16,17-double bond; or (b) halogen addition at the 16,17-double bond; or (c) epoxidation at the 16,17-double bond and optional reduction of the resulting epoxide to the C16-alcohol. Also claimed are: (A) the production of a 2,3-unsaturated epothilone N-oxide (IB) by: (i) N-oxidising a 3,7-protected epothilone A or B (IIB) in a known manner and eliminating the C3-substituent by base treatment; or (ii) N-oxidising a C7-optionally protected-2,3-unsaturated-epothilone A or B (IIC) in a known manner and optionally O-alkylating the resulting N-oxide in a known manner; (B) the production of an epothilone N-oxide (IC) by N-oxidising (IIA) in a known manner and optionally O-alkylating the resulting N-oxide in a known manner; (C) the production of a C19-(alkyl, aryl, heteroaryl, halo, oxygen or sulphur)-substituted epothilone (ID) by metallating ( IIA) at C19 and then reacting with an electrophile to introduce the C19 substituent; and (D) the production of a C27-hetero substituted epothilone (IE) by substituting the C27 methyl group by a heteroatom in a known manner. |
