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Dehaloperoxidase Catalyzed Stereoselective Synthesis of Cyclopropanol Esters
Siriboe, Mary G ; Vargas, David A ; Fasan, Rudi JOC,2022,88(12):7630-7640. DOI: 10.1021/acs.joc.2c02030 PubMed ID: 36542602
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Abstract: 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.
Purchased from AmBeed: 99-94-5 ; 100-09-4 ; 99-94-5 ; 403-42-9 ; 585-74-0 ; 709-63-7 ; 577-16-2 ; 99-90-1 ; 769-78-8 ; 931-48-6 ; 122-00-9 ; 946-39-4 ; 34702-96-0 ; 100-06-1 ; 16545-68-9 ; 2206-94-2 ; 88912-03-2 ; 946-38-3 ; 7605-25-6 ; 930-51-8 ; 20461-98-7 ; 5296-64-0 ; 99-90-1 ...More
CAS No. : | 769-78-8 | MDL No. : | MFCD00048141 |
Formula : | C9H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KOZCZZVUFDCZGG-UHFFFAOYSA-N |
M.W : | 148.16 | Pubchem ID : | 13037 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |