Intermolecular carbene S-H insertion catalysed by engineered myoglobin-based catalysts†.
Intermolecular carbene S-H insertion catalysed by engineered myoglobin-based catalysts†.
复制标题
DOI：
10.1039/c5sc00080g
复制
发表时间：
2015-04-01
期刊：
影响因子：
8.4
通讯作者：
Fasan R
中科院分区：
文献类型：
--
作者：
Tyagi V;Bonn RB;Fasan R
报道了通过分子间卡宾S-H插入反应合成硫醚的生物催化策略的第一个实例。报道了通过分子间卡宾S-H插入反应合成硫醚的生物催化策略的第一个实例。抹香鲸肌红蛋白的工程变体被发现可以有效地催化这种C-S键形成转化，跨越各种芳基和烷基底物和α-重氮酯卡宾供体，提供高转化率（60-99%）和高催化周转率（1100-5400）。此外，这些生物催化剂的对映体选择性可以通过突变的血红素蛋白的远端口袋内的氨基酸残基进行调整，导致肌红蛋白的变体能够支持不对称的S-H插入高达49%ee.Rearrangement实验支持一种机制，涉及形成一个锍叶立德的巯基底物的攻击后产生的血红素结合的卡宾中间体。
The first example of a biocatalytic strategy for the synthesis of thioethers via an intermolecular carbene S–H insertion reaction is reported. The first example of a biocatalytic strategy for the synthesis of thioethers via an intermolecular carbene S–H insertion reaction is reported. Engineered variants of sperm whale myoglobin were found to efficiently catalyze this C–S bond forming transformation across a diverse set of aryl and alkyl mercaptan substrates and α-diazoester carbene donors, providing high conversions (60–99%) and high numbers of catalytic turnovers (1100–5400). Furthermore, the enantioselectivity of these biocatalysts could be tuned through mutation of amino acid residues within the distal pocket of the hemoprotein, leading to myoglobin variants capable of supporting asymmetric S–H insertions with up to 49% ee. Rearrangement experiments support a mechanism involving the formation of a sulfonium ylide generated upon attack of the thiol substrate to a heme-bound carbene intermediate.