Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, United States.
J Am Chem Soc. 2020 Jun 10;142(23):10279-10283. doi: 10.1021/jacs.0c03428. Epub 2020 May 29.
Aliphatic primary amines are prevalent in natural products, pharmaceuticals, and functional materials. While a plethora of processes are reported for their synthesis, methods that directly install a free amine group into C(sp)-H bonds remain unprecedented. Here, we report a set of new-to-nature enzymes that catalyze the direct primary amination of C(sp)-H bonds with excellent chemo-, regio-, and enantioselectivity, using a readily available hydroxylamine derivative as the nitrogen source. Directed evolution of genetically encoded cytochrome P411 enzymes (P450s whose Cys axial ligand to the heme iron has been replaced with Ser) generated variants that selectively functionalize benzylic and allylic C-H bonds, affording a broad scope of enantioenriched primary amines. This biocatalytic process is efficient and selective (up to 3930 TTN and 96% ), and can be performed on preparative scale.
脂肪族伯胺广泛存在于天然产物、药物和功能材料中。尽管已有大量方法用于合成伯胺，但直接在 C(sp)-H 键上引入游离胺基的方法仍未见报道。在这里，我们报道了一组新型天然酶，它们可以使用易得的羟胺衍生物作为氮源，以优异的化学、区域和对映选择性催化 C(sp)-H 键的直接伯胺化反应。通过对基因编码细胞色素 P411 酶（其轴向配体到血红素铁的 Cys 已被 Ser 取代的 P450）的定向进化，生成了选择性官能化苄基和烯丙基 C-H 键的变体，得到了广泛的对映体富集的伯胺。该生物催化过程高效且选择性高（最高可达 3930 TTN 和 96%），可在制备规模上进行。
