Department of Medicinal Chemistry, University of Utah, 30 S 2000 E, Salt Lake City, Utah 84112, United States.
Chem Rev. 2021 Jun 23;121(12):6850-6914. doi: 10.1021/acs.chemrev.0c01013. Epub 2021 Jan 5.
Reactions that occur under physiological conditions find diverse uses in the chemical and biological sciences. However, the limitations that biological systems place on chemical reactions restrict the number of such bioorthogonal reactions. A profound understanding of the mechanistic principles and structure-reactivity trends of these transformations is therefore critical to access new and improved versions of bioorthogonal chemistry. The present article reviews the mechanisms and substituent effects of some of the principal metal-free bioorthogonal reactions based on inverse-electron demand Diels-Alder reactions, 1,3-dipolar cycloadditions, and the Staudinger reaction. Mechanisms of modified versions that link these reactions to a dissociative step are further discussed. The presented summary is anticipated to aid the advancement of bioorthogonal chemistry.
在生理条件下发生的反应在化学和生物科学中有着广泛的应用。然而，生物系统对化学反应的限制限制了这些生物正交反应的数量。因此，深刻理解这些转化的机械原理和结构反应趋势对于获得新的和改进的生物正交化学版本至关重要。本文综述了一些基于逆电子需求 Diels-Alder 反应、1,3-偶极环加成和施陶丁格反应的主要无金属生物正交反应的机制和取代基效应。进一步讨论了将这些反应与离解步骤联系起来的改进版本的机制。预计本文的总结将有助于生物正交化学的发展。
