Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
J Am Chem Soc. 2014 Jan 8;136(1):506-12. doi: 10.1021/ja411692v. Epub 2013 Dec 18.
Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here we report a novel bioinspired quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts.
铜胺氧化酶是一类含有醌辅因子的酶，可将伯胺氧化为醛。天然的反应机制经过亚氨醌中间体，从而对伯胺反应具有高选择性，从而限制了潜在仿生合成应用的范围。在这里，我们报告了一种新颖的受生物启发的醌催化剂体系，该体系由 1,10-菲咯啉-5,6-二酮/ZnI2 组成，该体系通过涉及半亚胺中间体的非生物途径绕过了这些限制。高效的有氧脱氢反应可用于非天然的仲胺底物，包括具有药用价值的氮杂环。ZnI2 共催化剂使醌对胺氧化作用活化，并提供碘化物的来源，碘化物在促进有氧催化循环中起着重要的氧化还原介质作用。这些发现为使用醌类催化剂的有氧氧化反应的更广泛发展提供了有价值的基础。
