Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis.
Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis.
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DOI：
10.1002/anie.201810059
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发表时间：
2018-11-26
期刊：
影响因子：
--
通讯作者：
Fasan R
中科院分区：
文献类型：
--
作者：
Chandgude AL;Fasan R
报道了一种高立体选择性合成腈取代环丙烷的化学生物催化策略。本发明的方法依赖于在隔室化反应系统内在非原位产生的重氮乙腈的存在下由工程化肌红蛋白催化的不对称烯烃环丙烷化反应。该方法能够以高达99.9%的de和ee和高达5，600次的周转率在制备规模下有效地转化宽范围的烯烃底物。酶促产物可以进一步加工以提供各种官能化的手性环丙烷。这项工作扩大了通过生物催化可获得的合成有价值的非生物转化的范围，并为重氮乙腈在生物催化卡宾转移反应中的实用和安全开发铺平了道路。一对多：涉及肌红蛋白催化的烯烃环丙烷化的化学生物催化策略，在异位生成的重氮乙腈的存在下，能够有效地合成具有高非对映体和对映体选择性的广泛的腈取代的环丙烷。酶促产物可以进一步加工以提供各种官能化的手性环丙烷。
A chemobiocatalytic strategy for the highly stereoselective synthesis of nitrile-substituted cyclopropanes is reported. The present approach relies on an asymmetric olefin cyclopropanation reaction catalyzed by an engineered myoglobin in the presence of ex situ generated diazoacetonitrile within a compartmentalized reaction system. This method enabled the efficient transformation of a broad range of olefin substrates at a preparative scale with up to 99.9% de and ee and up to 5,600 turnovers. The enzymatic product could be further elaborated to afford a variety of functionalized chiral cyclopropanes. This work expands the range of synthetically valuable, abiotic transformations accessible through biocatalysis and it paves the way to the practical and safe exploitation of diazoacetonitrile in biocatalytic carbene transfer reactions. One for many: A chemobiocatalytic strategy involving myoglobin-catalyzed olefin cyclopropanation in the presence of ex situ generated diazoacetonitrile enables the efficient synthesis of a broad range of nitrile-substituted cyclopropanes with high diastereo- and enantioselectivity. The enzymatic product could be further elaborated to afford a variety of functionalized chiral cyclopropanes.
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影响因子：
--
作者：
Ferrand, Y;Le Maux, P;Simonneaux, G
通讯作者：
Simonneaux, G
DOI：
10.1002/cbic.201500624
发表时间：
2016-03-02
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Gober JG;Rydeen AE;Gibson-O'Grady EJ;Leuthaeuser JB;Fetrow JS;Brustad EM
通讯作者：
Brustad EM
影响因子：
56.9
作者：
Coelho, Pedro S.;Brustad, Eric M.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.
影响因子：
2.7
作者：
Gauthier, Jacques Yves;Chauret, Nathalie;Black, W. Cameron
通讯作者：
Black, W. Cameron
影响因子：
14.8
作者：
Coelho PS;Wang ZJ;Ener ME;Baril SA;Kannan A;Arnold FH;Brustad EM
通讯作者：
Brustad EM