Scalable and selective deuteration of (hetero)arenes.
Scalable and selective deuteration of (hetero)arenes.
复制标题
DOI：
10.1038/s41557-021-00846-4
复制
发表时间：
2022-03
期刊：
影响因子：
21.8
通讯作者：
Beller M
中科院分区：
文献类型：
--
作者：
Li W;Rabeah J;Bourriquen F;Yang D;Kreyenschulte C;Rockstroh N;Lund H;Bartling S;Surkus AE;Junge K;Brückner A;Lei A;Beller M
同位素标记，特别是氘代，是开发新药的重要工具，特别是用于鉴定和定量代谢物。为此，已经开发了许多有效的方法，允许小规模合成选择性氘代化合物。由于氘化化合物作为活性药物成分的发展，人们对可扩展的氘化方法的兴趣越来越大。在工业环境中开发大规模氘标记方法需要可靠、稳健和可扩展的技术。在这里，我们表明，纳米结构的铁催化剂，制备纤维素与丰富的铁盐相结合，允许选择性氘化（杂）芳烃，包括苯胺，苯酚，吲哚和其他杂环，使用廉价的D2O在氢气压力下。这种方法代表了一种易于扩展的氘化（通过在千克规模上合成含氘产品来证明），并且空气和水稳定的催化剂能够以简单的方式进行高效标记，并具有高质量控制。发展了一种苯胺、吲哚、酚和杂环化合物（包括天然产物和其它生物活性分子）的选择性氘代方法。支撑这一过程的纳米结构铁催化剂是通过将纤维素与铁盐结合来制备的，并已用于制备高达千克规模的氘代化合物。
Isotope labelling, particularly deuteration, is an important tool for the development of new drugs, specifically for identification and quantification of metabolites. For this purpose, many efficient methodologies have been developed that allow for the small-scale synthesis of selectively deuterated compounds. Due to the development of deuterated compounds as active drug ingredients, there is a growing interest in scalable methods for deuteration. The development of methodologies for large-scale deuterium labelling in industrial settings requires technologies that are reliable, robust and scalable. Here we show that a nanostructured iron catalyst, prepared by combining cellulose with abundant iron salts, permits the selective deuteration of (hetero)arenes including anilines, phenols, indoles and other heterocycles, using inexpensive D2O under hydrogen pressure. This methodology represents an easily scalable deuteration (demonstrated by the synthesis of deuterium-containing products on the kilogram scale) and the air- and water-stable catalyst enables efficient labelling in a straightforward manner with high quality control. A method for the selective deuteration of anilines, indoles, phenols and heterocyclic compounds, including natural products and other bioactive molecules, has been developed. The nanostructured iron catalyst that underpins this process is prepared by combining cellulose with iron salts and has been used for the preparation of deuterated compounds on up to a kilogram scale.
登录
查看更多内容
影响因子：
56.9
作者：
Jagadeesh, Rajenahally V.;Surkus, Annette-Enrica;Beller, Matthias
通讯作者：
Beller, Matthias
影响因子：
4.5
作者：
Mueller, Valentin;Weck, Remo;Ackermann, Lutz
通讯作者：
Ackermann, Lutz
影响因子：
1.8
作者：
Heys, J. Richard
通讯作者：
Heys, J. Richard
影响因子：
4
作者：
Ito, Nobuhiro;Esaki, Hiroyoshi;Sajiki, Hironao
通讯作者：
Sajiki, Hironao
影响因子：
1.8
作者：
Czeskis, Boris;Elmore, Charles S.;Wang, Peng
通讯作者：
Wang, Peng