ABSTRACT

Microreaction and membrane technologies offer optimal conditions for controlling enantiomer synthesis and purification processes in continuous production, with numerous advantages over batch manufacturing. One of the many forces driving the development of such technologies for the production of single optical isomers is the need for enantiomerically pure pharmaceutical drugs because enantiomers may display opposite therapeutic effects or different treatment efficacies and side effects. Yet, despite advances in asymmetric synthesis and separation techniques, preparing enantiomerically pure compounds remains a challenging task. Here, we review the progress in microfluidics and membrane chiral separation over the last two decades. In addition to describing and critically assessing the state of the art in both disciplines, we provide an overview of their beneficial properties and characteristics for developing technologies toward producing enantiomerically pure compounds. Concomitantly, we evaluate efforts to integrate synthesis and membrane separation into a microfluidic platform and pinpoint the limiting factors that must be overcome before these platforms can be fully deployed in the industry.

摘要

微反应和膜技术为连续生产中控制对映体合成和纯化过程提供了最佳条件，与批量生产相比具有许多优势。推动此类单一光学异构体生产技术发展的众多力量之一是对对映体纯药物的需求，因为对映体可能表现出相反的治疗效果或不同的治疗功效和副作用。然而，尽管不对称合成和分离技术取得了进步，制备对映体纯的化合物仍然是一项具有挑战性的任务。在这里，我们回顾了过去二十年微流体和膜手性分离的进展。除了描述和批判性评估这两个学科的最新技术之外，我们概述了它们的有益特性和特征，用于开发生产对映体纯化合物的技术。与此同时，我们评估了将合成和膜分离集成到微流体平台中的努力，并查明这些平台在行业中全面部署之前必须克服的限制因素。