Department of Organic and Inorganic Chemistry, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain.
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
Molecules. 2022 Dec 29;28(1):271. doi: 10.3390/molecules28010271.
Majority of drugs act by interacting with chiral counterparts, e.g., proteins, and we are, unfortunately, well-aware of how chirality can negatively impact the outcome of a therapeutic regime. The number of chiral, non-racemic drugs on the market is increasing, and it is becoming ever more important to prepare these compounds in a safe, economic, and environmentally sustainable fashion. Asymmetric organocatalysis has a long history, but it began its renaissance era only during the first years of the millennium. Since then, this field has reached an extraordinary level, as confirmed by the awarding of the 2021 Chemistry Nobel Prize. In the present review, we wish to highlight the application of organocatalysis in the synthesis of enantio-enriched molecules that may be of interest to the pharmaceutical industry and the medicinal chemistry community. We aim to discuss the different activation modes observed for organocatalysts, examining, for each of them, the generally accepted mechanisms and the most important and developed reactions, that may be useful to medicinal chemists. For each of these types of organocatalytic activations, select examples from academic and industrial applications will be disclosed during the synthesis of drugs and natural products.
大多数药物通过与手性对应物（例如蛋白质）相互作用发挥作用，不幸的是，我们深知手性如何会对治疗方案的结果产生负面影响。市场上手性、非外消旋药物的数量正在增加，以安全、经济和环境可持续的方式制备这些化合物变得越来越重要。不对称有机催化有着悠久的历史，但直到千禧年的最初几年才开始复兴。从那时起，该领域达到了非凡的水平，这一点得到了 2021 年诺贝尔化学奖的肯定。在本次综述中，我们希望强调有机催化在手性富集分子合成中的应用，这些分子可能引起制药行业和药物化学界的兴趣。我们旨在讨论观察到手性催化剂的不同活化模式，对于每一种模式，我们都研究了普遍接受的机制以及最重要和最发达的反应，这些反应可能对药物化学家有用。对于这些类型的有机催化活化中的每一种，在药物和天然产物的合成过程中，将披露来自学术和工业应用的选择示例。
