通过基质氨基转移方法对Sacubitril的立体选择性合成的研究
Megha V Sadanande1,2, Sagar S Thorat1,2, Himanshu Sharma2,3
1Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.
Chemistry, an Asian journal
|December 23, 2024
概括
我们开发了新型合成路径,用于sacubitril,一个关键的 neprilysin 抑制剂. 这些方法利用奇拉氨基转移试剂进行高效的立体选择性合成,改善药物制造.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 制药合成 制药合成
背景情况:
- 萨库比特里尔是一种关键的 neprilysin 抑制剂,通常与 valsartan 结合在 Entresto TM 中治疗心力衰竭.
- 在制药生产中,高效和立体选择性合成sacubitril至关重要.
研究的目的:
- 详细介绍了sacubitril的合成策略. 为了详细说明sacubitril的合成策略.
- 探索基于合池和合氨基转移 (CAT) 的方法.
- 为了优化sacubitril合成中的立体化学控制.
主要方法:
- 最初的合成采用了用 (S) - 铁酸和Cu (I) 介导的交叉合的性池策略.
- 开发了一种使用奇拉胺转移 (CAT) 试剂的立体选择性合成.
- 关键步骤包括E-选择性布特化物构造,ene-lactam形成和 diastereoselective 减少.
主要成果:
- 通过两种不同的策略成功合成了sacubitril.
- 证明了CAT试剂在立体选择性合成中的有效性.
- 在DFT研究中,为降低乳的立体化学结果提供了合理化.
结论:
- 开发的基于CAT试剂的合成提供了一条有效的途径到sacubitril.
- 这项研究有助于推进立体选择性合成方法的发展.
- 优化合成途径对于可扩展的sacubitril生产至关重要.
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