Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Chemistry. 2024 Oct 8;30(56):e202402380. doi: 10.1002/chem.202402380. Epub 2024 Sep 12.
N-heterocyclic compounds have a broad range of applications and their selective synthesis is very appealing for the pharmaceutical and agrochemical industries. Herein we report the usage of the flavin-dependent nitroreductase BaNTR1 for the photoenzymatic synthesis of various anthranils and quinolines from retro-synthetically designed o-nitrophenyl-substituted carbonyl substrates, achieving high conversions (up to >99 %) and good product yields (up to 96 %). Whereas the effective production of anthranils required the inclusion of HO in the reaction mixtures to accumulate the needed hydroxylamine intermediates, the formation of quinolines required the use of anaerobic or reducing conditions to efficiently generate the essential amine intermediates. Critical to our success was the high chemoselectivity of BaNTR1, performing selective reduction of the nitro group without reduction of the carbonyl moiety or the activated carbon-carbon double bond. The results highlight the usefulness of an innocuous chlorophyll- and nitroreductase-based photoenzymatic system for the tailored synthesis of diverse N-heterocycles from simple nitro compounds.
杂环化合物具有广泛的应用，其选择性合成对制药和农用化学品行业非常有吸引力。在此，我们报告了黄素依赖型硝基还原酶 BaNTR1 在光酶合成方面的应用，该酶可将经过反合成设计的邻硝基苯取代的羰基底物转化为各种邻氨基苯甲酸和喹啉，转化率高（高达＞99％），产率好（高达 96％）。虽然有效生产邻氨基苯甲酸需要在反应混合物中加入 HO 来积累所需的羟胺中间体，但形成喹啉需要使用厌氧或还原条件来有效地生成必需的胺中间体。我们成功的关键是 BaNTR1 的高化学选择性，其可选择性还原硝基，而不还原羰基部分或活化的碳-碳双键。结果突出了基于无害叶绿素和硝基还原酶的光酶系统在从简单的硝基化合物定制合成各种杂环化合物方面的有用性。
