Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
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DOI：
10.1002/anie.201812968
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发表时间：
2019-03-04
影响因子：
16.6
通讯作者：
Arnold, Frances H.
中科院分区：
文献类型：
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作者：
Cho, Inha;Prier, Christopher K.;Arnold, Frances H.
手性1,2-氨基醇广泛存在于从神经递质到抗病毒药物的生物活性化合物中。虽然已经开发了许多合成方法来获取氨基醇，但将烯烃直接氨基羟基化为无保护的、对映体富集的氨基醇仍然是一个挑战。利用定向进化，我们设计了一种基于耐热细胞色素c的血红蛋白生物催化剂，该催化剂在厌氧条件下以o -戊酰羟胺作为胺化试剂，直接将烯烃转化为具有高对映选择性（高达2500 TTN和90% ee）的氨基醇。该反应是通过酶活性位点产生的活性铁氮来进行的，从而可以通过蛋白质工程调节催化剂的活性和选择性。
Chiral 1,2-amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O-pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron-nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.