抗肿瘤药物盐酸伊达比星的绿色制备方法

A green preparation method of the antitumor drug idarubicin hydrochloride

目的本论文主要进行了蒽环类抗肿瘤药物盐酸伊达比星绿色制备工艺的研究。方法与结果首先起始原料柔红霉素与三氟乙酸乙酯反应得到中间体1,采用金属镍催化剂/有机膦配体/硅烷还原剂一步脱除蒽环类化合物4-位甲氧基,在碱性条件下脱保护基成盐得到盐酸伊达比星。结论该工艺大大缩短反应步骤及降低合成成本,避免传统半合成工艺带来的有毒有害试剂使用,适合工业化放大,绿色环保。制备总收率为57.0%,纯度为99.5%。

Objective In this paper the green synthesis of anthracyclines anti-tumor drug idarubicin was mainly investigated.Method and Result The starting material daunorubicin was reacted with the ethyl trifluoroacetate to obtain intermediate 1,followed by one-step removal of 4-methoxy group of anthracycline compounds utilizing nickelcatalyst,organophosphine ligands and silane reducing agent.Subsequently,the protective group was removed under basic conditions to obtain idarubicin hydrochloride.Conclusions Our findings predominantly shorten the synthetic route,reduces the synthetic cost and avoids the use of toxic/harmful reagents in traditional semi-synthesis,which would be suitable for industrial scale-up as well as environmental protection.The total yield was 57.0%,and the purity was 99.5%.