Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.
Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.
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DOI：
10.1002/anie.201601056
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发表时间：
2016-04-04
期刊：
影响因子：
--
通讯作者：
Arnold FH
中科院分区：
文献类型：
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作者：
Prier CK;Hyster TK;Farwell CC;Huang A;Arnold FH
异位重排虽然在生物学中很少见，但却为复杂化学基序的高效和选择性合成提供了机会。细胞色素P450BM3的“P411”丝氨酸连接变体已被设计用于在整个大肠杆菌细胞中启动硫酰化/[2,3]-异位重排序列，这对任何酶来说都是一种非自然功能，提供了对乙酰氨基富集，受保护的烯丙基胺。该酶的五个突变极大地增强了其对这种新功能的活性，证明了该催化剂对挑战亚硝基转移反应的可进化性。所进化的催化剂还能对非烯丙基硫化物进行高度对映选择性的模拟。
Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine-ligated variant of cytochrome P450BM3 has been engineered to initiate a sulfimidation/[2,3]-sigmatropic rearrangement sequence in whole E. coli cells, a non-natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non-allylic sulfides.