公开(公告)号：US20100274031A1

公开(公告)日：2010-10-28

申请号：US12768014

申请日：2010-04-27

Applicant: Olga Tsubrik ,  Andrus Tasa ,  Ain Uustare ,  Ago Rinken ,  Uno Mäeorg ,  Kristiina Ylihonko ,  Maria Holmbäck ,  Jukka Raunio

Inventor： Olga Tsubrik ,  Andrus Tasa ,  Ain Uustare ,  Ago Rinken ,  Uno Mäeorg ,  Kristiina Ylihonko ,  Maria Holmbäck ,  Jukka Raunio

IPC: C07D309/10

CPC classification number: C07D309/10

Abstract: 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.

Abstract translation: 生产氨柔比星的方法及其结构类似物。 本发明包括用于生产氨柔比星（式I）及其结构类似物的合成途径。 本发明的合成途径优选使用具有通式II的蒽环类化合物作为起始物质：式II化合物可以具有以下特征的任意组合：R1，R2，R3，R4和R8可以 为H，OH或烷氧基; R5可以是H，烷基或烷氧基羰基; R6可以是H或烷基; R 7可以是OH或烷基。 在某些实施方案中，可以使用霉素霉素酮或道诺霉素酮作为根据式II的原料。 本发明使用式II化合物作为将传统化学合成步骤与生物合成步骤结合以产生氨柔比星，其衍生物及其结构类似物的半合成方法的一部分。 本发明的方法优选包括糖基化反应，由此将氨柔比星或其结构类似物的脂肪糖糖基化以产生最终产物。