Crystallizing Fats? Development of a Scalable, Chromatography-Free Synthesis of Cationic Lipids,Organic Process Research & Development

当前位置： X-MOL 学术 › Org. Process Res. Dev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Crystallizing Fats? Development of a Scalable, Chromatography-Free Synthesis of Cationic Lipids
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-10-19 , DOI: 10.1021/acs.oprd.0c00374
Gregory L. Beutner ₁ , Sloan Ayers ₁ , Shawn Brueggemeier ₁ , Patricia Cho ₁ , Ronald Carrasquillo-Flores ₁ , Kathleen Kelly ₁ , Federico Lora Gonzalez ₁ , Jonathan Marshall ₁ , Subha Mukherjee ₁ , Jun Qiu ₁ , Michael J. Smith ₁

Affiliation

Research on the development of scalable routes to pharmaceutical intermediates typically proceeds from explorations of the chemistry to the identification of robust procedures for isolation. Although this order of investigation works well for typical small molecules possessing favorable physical properties and, therefore, numerous options for isolation, this is not always the case. The synthesis of cationic lipids is an exception to the rule and challenges this logic. Supported by extensive solubility and salt screening, we engaged in a reverse development effort, focusing first on identifying isolation conditions and then using that information to select appropriate chemistry. This strategy allowed for development of a robust, chromatography-free route to the cationic lipids of interest that was implemented at kilogram scale with quantifiable improvements to yield and efficiency when compared to the original route.

中文翻译：

结晶脂肪？阳离子脂质的可扩展，无色谱合成方法的开发

对药物中间体可扩展路线的开发研究通常是从化学探索到确定可靠的分离程序进行的。尽管此检查顺序对于具有良好物理特性的典型小分子非常有效，因此有许多隔离的选择，但情况并非总是如此。阳离子脂质的合成是该规则的例外，并挑战了这一逻辑。在广泛的溶解度和盐分筛选的支持下，我们进行了反向开发工作，首先致力于确定分离条件，然后使用该信息来选择合适的化学物质。通过该策略，我们可以开发出功能强大，

更新日期：2020-11-21

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11