生物加工过程2024，Vol.22Issue(1)：75-80,6.DOI:10.3969/j.issn.1672-3678.2024.01.010
骨质疏松症治疗药唑来膦酸的合成工艺改进
Improved synthesis of osteoporosis drug zoledronic acid
罗君陶 1王新仙 2卢定强3
作者信息
- 1. 南京工业大学药学院,江苏南京 211800
- 2. 江苏省药物研究所有限公司,江苏南京 211800
- 3. 南京工业大学药学院,江苏南京 211800||江苏省药物研究所有限公司,江苏南京 211800
- 折叠
摘要
Abstract
With the issue of aging population in our country,osteoporosis is becoming a more and more serious age-related disease.Zoledronic acid,which can significantly inhibit the bone absorption of bone-breaking cells,is the preferred drug for bone repair therapy to treat pain caused by osteoporosis.Herein we described the optimization of a synthetic route towards zoledronic acid,and our new process,with imidazole and ethyl chloroacetate as the two starting materials,proved to be highly reliable and environmentally friendly,along with simple operations.Upon the N-alkylation of imidazole with chloroacetate,the resultant ester was hydrolyzed to give imidazole acetic acid,which subsequently underwent phosphorylation by treatment with phosphorus oxychloride(POCl3)to afford the desired product zoledronic acid.After a variety of conditions were screened for the two key transformations,N-alkylation and phosphorylation,the final step was conducted at 75 ℃ using solid phosphorous acid(H3PO3)as solvent,with imidazole acetic acid and POCl3 at the ratio of 1.0∶2.2.The overall yield of our new approach was 43.55％,and the HPLC analysis of final product zoledronic acid showed 99.97％purity,which met the quality standards stipulated by the European Pharmacopoeia.关键词
唑来膦酸/合成/路线优化/骨质疏松症Key words
zoledronic acid/synthesis process/route optimization/osteoporosis分类
医药卫生引用本文复制引用
罗君陶,王新仙,卢定强..骨质疏松症治疗药唑来膦酸的合成工艺改进[J].生物加工过程,2024,22(1):75-80,6.
