合成途径的发展导致药品和关键中间体使用氧酸酶
Joy Chakraborty1, Genji Iwasaki1, Yasuhisa Asano1
1Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
The Journal of organic chemistry
|May 22, 2025
概括
这项研究引入了新的合成途径,使用Parafontaria laminata hydroxynitrile lyase (PlamHNL) 用于诸如Cenobamate和Clopidogrel之类的药物. 这些新的方法实现了优异的enantioselectivity,regioselectivity,以及关键药物中间体的产量.
科学领域:
- 生物催化和有机合成
- 酶工程用于制药生产的酶工程.
- 奇拉药物的不对称合成
背景情况:
- 氨酸酸酶 (HNLs) 是合成性构建块的关键酶.
- 现有的合成途径,如Cenobamate和Clopidogrel等药物,可以在效率和选择性上受到限制.
- 酸酸酸酶 (PlamHNL) 呈现出一种潜在的生物催化剂,用于改善药物合成.
研究的目的:
- 开发使用PlamHNL的活性药物成分 (API) 的新型合成途径.
- 在关键药物中间体的合成中增强酶选择性和区域选择性.
- 为了提高Cenobamate (Xcopri),Clopidogrel (Plavix) 和Mirabegron (Myrbetriq) 的生产总产量.
主要方法:
- 使用PlamHNL进行性曼德拉酸的不对称合成.
- 从HNL催化反应开始开发了新的合成途径.
- 优化反应条件,以实现高选择性和目标API的产量.
主要成果:
- 在HNL催化反应中实现了高的反抗选择性和区域选择性.
- 从常见的中间体, (R) - 甲基-2-曼德拉酸盐中演示了切诺巴和克洛皮多格勒的高效合成.
- 报告了Xcopri,Plavix和Myrbetriq的合成产量的改善.
结论:
- PlamHNL是一种有效的生物催化剂,用于开发重要的药物新型和高效的合成途径.
- 与现有方法相比,开发的方法在选择性和收益方面具有显著的优势.
- 这项工作为PlamHNL在API制造中的工业应用提供了基础.
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