利用含烯烃的底物构建取代的哌啶环，研究亮氨酸 5-羟化酶的替代反应。
Alternative Reactivity of Leucine 5-Hydroxylase Using an Olefin-Containing Substrate to Construct a Substituted Piperidine Ring.
机构信息
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
出版信息
Biochemistry. 2020 Jun 2;59(21):1961-1965. doi: 10.1021/acs.biochem.0c00289. Epub 2020 May 18.
Abstract
Applying enzymatic reactions to produce useful molecules is a central focus of chemical biology. Iron and 2-oxoglutarate (Fe/2OG) enzymes are found in all kingdoms of life and catalyze a broad array of oxidative transformations. Herein, we demonstrate that the activity of an Fe/2OG enzyme can be redirected when changing the targeted carbon hybridization from sp to sp. During leucine 5-hydroxylase catalysis, installation of an olefin group onto the substrate redirects the Fe(IV)-oxo species reactivity from hydroxylation to asymmetric epoxidation. The resulting epoxide subsequently undergoes intramolecular cyclization to form the substituted piperidine, 2,5-hydroxypipecolic acid.
摘要
将酶反应应用于生产有用的分子是化学生物学的一个核心关注点。铁和 2-氧戊二酸（Fe/2OG）酶存在于所有生命领域，催化广泛的氧化转化。在此，我们证明当改变目标碳杂化从 sp 到 sp 时，Fe/2OG 酶的活性可以被重新定向。在亮氨酸 5-羟化酶催化过程中，将烯烃基团安装到底物上会使 Fe(IV)-氧物种的反应性从羟化作用转向不对称环氧化作用。所得环氧化物随后进行分子内环化形成取代的哌啶，2,5-羟基哌啶酸。
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