| 童曦,陶晴丽,刘凤瑞,唐凤翔.化学通报,2018,81(2):116-121. |
| 治疗慢性淋巴细胞白血病的突破性新药Venetoclax的合成进展 |
| Advances in the Synthesis of Venetoclax as a New Cancer Drug for Chronic Lymphocytic Leukemia |
| 投稿时间：2017-07-27 修订日期：2017-10-27 |
| DOI： |
| 中文关键词: 慢性淋巴细胞白血病，Venetoclax，合成 |
| 英文关键词:Chronic lymphocytic leukemia, Venetoclax, Synthesis |
| 基金项目:福建省中青年教师教育科研项目（JAS151245）,福建省及福州大学创新创业教育改革项目联合资助。 |
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| 中文摘要: |
| Venetoclax为首个获美国FDA批准的靶向B细胞淋巴瘤因子2的选择性抑制剂和突破性药物,用于治疗携带 17p 删除突变以及之前已接受至少一种疗法的慢性淋巴细胞白血病。本文综述了迄今为止文献报道的venetoclax的4条合成工艺路线,并进行了相应的评价。通过对这些合成工艺路线的比较和分析,发现venetoclax的合成为汇聚式,关键在于4类中间体的合成。从venetoclax的合成工艺路线改进来看,其合成工艺路线总体上向着采用价廉易得原料、反应选择性高的原料或合成方式、更加温和的反应条件以及提高收率的方向进行。Venetoclax的4条合成工艺路线不可避免地采用了贵重金属钯和配体催化,探索将它们负载在高聚物上,便于回收这些贵重催化剂,简化分离过程和降低成本,也是venetoclax工业化合成改进的方向。在此基础上,venetoclax的合成路线4具有较好的工业化前景。 |
| 英文摘要: |
| Venetoclax, the first selective inhibitor of B-cell lymphoma-2, was approved by FDA for treating relapsed or refractory chronic lymphocytic leukemia patients with 17p deletion who have received at least one prior therapy. In this paper, four reported synthesis routes of venetoclaxare reviewed.The comparison andanalysis of these synthesis routes shows that convergentstrategiesare often applied in the synthesisofVenetoclax, and it includes the synthesis of four kinds of key intermediates. The synthesis routes of Venetoclaxare continuously improved in these respects of using cheap and readily available raw materials,raw materials or synthesis approaches with higher reaction selectivity, milder reaction conditions and enhancing gross yields. In view of the fact that all of the four synthesis routes involves precious metal (palladium) and ligands as catalysts, investigation of polymer-supported palladium and ligands as catalysts will simplify the recovery of catalysts and separation process, and further decrease the preparation cost. This also helps to the development of sustainable industrial production of Venetoclax. If this improvement is accomplished, the fourth synthesis route of Venetoclax has the greatest potential for industrialization. |
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