Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes
Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes
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DOI：
10.1126/science.1231434
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发表时间：
2013-01-18
期刊：
影响因子：
56.9
通讯作者：
Arnold, Frances H.
中科院分区：
文献类型：
--
作者：
Coelho, Pedro S.;Brustad, Eric M.;Arnold, Frances H.
过渡金属催化的卡宾、氮宾和氧烯的转移是功能化 C = C 和 C-H 键的有效方法。大自然已经进化出了用于牛转移的多样化工具箱，细胞色素 P450 酶催化的无数单氧化反应就是例证。等电子卡宾转移到烯烃是有机合成中广泛使用的 C-C 键形成反应，没有生物对应物。在这里，我们报道了细胞色素 P450（BM3）的工程变体，其通过推定的卡宾转移催化来自重氮酯试剂的苯乙烯的高度非对映和对映选择性环丙烷化。这项工作强调了利用现有酶来催化以前在自然界中未观察到的重要合成反应的能力。
Transition metal-catalyzed transfers of carbenes, nitrenes, and oxenes are powerful methods for functionalizing C = C and C-H bonds. Nature has evolved a diverse toolbox for oxene transfers, as exemplified by the myriad monooxygenation reactions catalyzed by cytochrome P450 enzymes. The isoelectronic carbene transfer to olefins, a widely used C-C bond-forming reaction in organic synthesis, has no biological counterpart. Here we report engineered variants of cytochrome P450(BM3) that catalyze highly diastereo- and enantioselective cyclopropanation of styrenes from diazoester reagents via putative carbene transfer. This work highlights the capacity to adapt existing enzymes for the catalysis of synthetically important reactions not previously observed in nature.