Dehaloperoxidase Catalyzed Stereoselective Synthesis of Cyclopropanol Esters.
Dehaloperoxidase Catalyzed Stereoselective Synthesis of Cyclopropanol Esters.
复制标题
DOI：
10.1021/acs.joc.2c02030
复制
发表时间：
2023-06-16
影响因子：
3.6
通讯作者：
Fasan, Rudi
中科院分区：
文献类型：
--
作者：
Siriboe, Mary G.;Vargas, David A.;Fasan, Rudi
手性环丙醇是药物化学中非常理想的结构单元，但这些分子的立体选择性合成仍然具有挑战性。在这里，报道了一种新的策略，通过生物催化的不对称环丙烷化乙烯基酯与重氮乙酸乙酯（EDA）的非对映体和对映体选择性合成环丙醇衍生物。来自装饰双眉藻的脱卤过氧化物酶被重新用于催化这种具有挑战性的环丙烷化反应，并且通过蛋白质工程优化其活性和立体选择性。使用该系统，广泛的缺电子乙烯基酯被有效地转化为所需的环丙烷化产物，非对映异构体和对映异构体的比例高达99.5：0.5。此外，工程化的基于脱卤过氧化物酶的生物催化剂能够催化各种其他非生物卡宾转移反应，包括用EDA进行的N-H/S-H卡宾插入以及用重氮乙腈进行的环丙烷化，从而增加了这种酶的多功能性，并将其定义为用于开发新型卡宾转移酶的有价值的新支架。
Chiral cyclopropanols are highly desirable building blocks for medicinal chemistry, but the stereoselective synthesis of these molecules remains challenging. Here, a novel strategy is reported for the diastereo- and enantioselective synthesis of cyclopropanol derivatives via the biocatalytic asymmetric cyclopropanation of vinyl esters with ethyl diazoacetate (EDA). A dehaloperoxidase enzyme from Amphitrite ornata was repurposed to catalyze this challenging cyclopropanation reaction, and its activity and stereoselectivity were optimized via protein engineering. Using this system, a broad range of electron-deficient vinyl esters were efficiently converted to the desired cyclopropanation products with up to 99.5:0.5 diastereomeric and enantiomeric ratios. In addition, the engineered dehaloperoxidase-based biocatalyst is able to catalyze a variety of other abiological carbene transfer reactions, including N–H/S–H carbene insertion with EDA as well as cyclopropanation with diazoacetonitrile, thus adding to the multifunctionality of this enzyme and defining it as a valuable new scaffold for the development of novel carbene transferases.
登录
查看更多内容
DOI：
10.1002/anie.201810059
发表时间：
2018-11-26
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Chandgude AL;Fasan R
通讯作者：
Fasan R
影响因子：
5.4
作者：
D'Antonio, Edward L.;Chen, Thomas K.;Bowden, Edmond F.
通讯作者：
Bowden, Edmond F.
DOI：
10.1016/j.bbrc.2004.09.174
发表时间：
2004-11-26
影响因子：
3.1
作者：
Osborne, RL;Taylor, LO;Dawson, JH
通讯作者：
Dawson, JH
影响因子：
15
作者：
Barrios, David A.;D'Antonio, Jennifer;McCombs, Nikolette L.;Zhao, Jing;Franzen, Stefan;Schmidt, Andreas C.;Sombers, Leslie A.;Ghiladi, Reza A.
通讯作者：
Ghiladi, Reza A.
影响因子：
2.9
作者：
Du, Jing;Huang, Xiao;Dawson, John H.
通讯作者：
Dawson, John H.