Methods for producing amrubicin and structural analogs thereof. The present invention encompasses synthetic pathways for the production of amrubicin (Formula I) and structural analogs thereof. The synthetic pathways of the present invention preferably employ as a starting material an anthracycline compound having the generic Formula (II): Compounds of Formula II may have any combination of the following identities for the indicated moieties: R1, R2, R3, R4, and R8 may be H, OH, or alkoxy; R5 may be H, alkyl, or alkoxycarbonyl; R6 may be H or alkyl; R7 may be OH or alkyl. In certain embodiments, ε-rhodomycinone or daunomycinone may be used as starting materials according to Formula (II). The present invention employs a compound of Formula (II) as part of a semi-synthetic method that combines traditional chemical synthetic steps with biosynthetic steps to produce amrubicin, derivatives thereof, and structural analogs thereof. The methods of the present invention preferably include a glycosylation reaction whereby an algycon of amrubicin or structural analog thereof is glycosylated to produce the final product.
生产阿姆鲁比辛及其结构类似物的方法。本发明涵盖了用于生产阿姆鲁比辛(
化学式I)及其结构类似物的合成途径。本发明的合成途径通常使用具有通用
化学式(II)的
蒽喜树碱化合物作为起始物质:化合物II的各个部分可能具有以下标识:R1、R2、R3、R4和R8可能是H、OH或烷氧基;R5可能是H、烷基或烷氧羰基;R6可能是H或烷基;R7可能是OH或烷基。在某些实施例中,ε-罗多霉素酮或多诺霉素酮可以按照
化学式(II)作为起始材料。本发明采用
化学式(II)的化合物作为半合成方法的一部分,将传统的
化学合成步骤与
生物合成步骤相结合,以生产阿姆鲁比辛、其衍
生物和结构类似物。本发明的方法通常包括一种糖基化反应,通过该反应,阿姆鲁比辛的糖基化物或其结构类似物的糖基化物被合成为最终产物。