Enantioselective Bioreduction of Medicinally Relevant Nitrogen-Heteroaromatic Ketones,ACS Medicinal Chemistry Letters

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Enantioselective Bioreduction of Medicinally Relevant Nitrogen-Heteroaromatic Ketones
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2023-05-10 , DOI: 10.1021/acsmedchemlett.3c00114
Wen-Ju Bai ₁ , Michelle A Estrada ₁ , Jackson A Gartman ₁ , Andrew S Judd ₁

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We herein report an enantioselective bioreduction of ketones that bear the most frequently used nitrogen-heteroaromatics in FDA-approved drugs. Ten varieties of these nitrogen-containing heterocycles were systematically investigated. Eight categories were studied for the first time and seven types were tolerated, significantly expanding the substrate scope of plant-mediated reduction. By use of purple carrots in buffered aqueous media with a simplified reaction setup, this biocatalytic transformation was achieved within 48 h at ambient temperature, offering medicinal chemists a pragmatic and scalable tool to access a broad variety of nitrogen-heteroaryl-containing chiral alcohols. With multiple reactive sites, the structurally diverse set of chiral alcohols can be used for library compound preparation, early route-scouting activities, and synthesis of other pharmaceutical molecules, favorably accelerating medicinal chemistry campaigns.

中文翻译：

医学相关氮杂芳酮的对映选择性生物还原

我们在此报告了 FDA 批准的药物中最常用的含氮杂芳烃的酮的对映选择性生物还原。对这些含氮杂环的十个品种进行了系统研究。首次研究八类，七类耐受，显着扩大了植物介导还原的底物范围。通过在缓冲水介质中使用紫胡萝卜并采用简化的反应装置，这种生物催化转化在环境温度下在 48 小时内实现，为药物化学家提供了一种实用且可扩展的工具来获取各种含氮杂芳基的手性醇。凭借多个反应位点，结构多样的手性醇可用于库化合物制备、早期路线探索活动以及其他药物分子的合成，从而有利地加速药物化学活动。

更新日期：2023-05-10

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