Catalytic Deuterium Incorporation within Metabolically Stable β-Amino C–H Bonds of Drug Molecules,Journal of the American Chemical Society

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Catalytic Deuterium Incorporation within Metabolically Stable β-Amino C–H Bonds of Drug Molecules
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2019-09-03 , DOI: 10.1021/jacs.9b08662
Yejin Chang ₁ , Ahmet Yesilcimen ₁ , Min Cao ₁ , Yuyang Zhang ₁ , Bochao Zhang ₁ , Jessica Z Chan ₁ , Masayuki Wasa ₁

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An efficient deuteration process of beta-amino C-H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C6F5)3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of beta-deuterated bioactive amines with up to 99% deuterium incorporation.

中文翻译：

药物分子代谢稳定的 β-氨基 C-H 键中的催化氘掺入

已开发出各种基于 N-烷基胺的药物化合物中 β-氨基 CH 键的有效氘化过程。催化反应开始于路易斯酸性 B(C6F5)3 和布朗斯台德碱性 N-烷基胺的作用，将药物分子转化为相应的烯胺。酸/碱催化剂还促进丙酮-d6 的氘化以提供氘化铵离子。随后烯胺的氘化会导致β-氘化生物活性胺的形成，其中氘掺入量高达 99%。

更新日期：2019-09-03

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