Chemoenzymatic synthesis of optically active α-cyclopropyl-pyruvates and cyclobutenoates via enzyme-catalyzed carbene transfer with diazopyruvate.
| Autor: | Dollet R; INSA Rouen Normandie, Univ Rouen Normandie, CNRS, Normandie Univ, COBRA UMR 6014, INC3M FR 3038, F-76000 Rouen, France., Villada JD; Department of Chemistry and Biochemistry, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080 (USA)., Poisson T; INSA Rouen Normandie, Univ Rouen Normandie, CNRS, Normandie Univ, COBRA UMR 6014, INC3M FR 3038, F-76000 Rouen, France., Fasan R; Department of Chemistry and Biochemistry, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080 (USA)., Jubault P; INSA Rouen Normandie, Univ Rouen Normandie, CNRS, Normandie Univ, COBRA UMR 6014, INC3M FR 3038, F-76000 Rouen, France. |
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| Jazyk: | angličtina |
| Zdroj: | Organic chemistry frontiers : an international journal of organic chemistry [Org Chem Front] 2024 Apr 07; Vol. 11 (7), pp. 2008-2014. Date of Electronic Publication: 2024 Feb 07. |
| DOI: | 10.1039/d3qo01987j |
| Abstrakt: | Cyclopropanes are recurrent structural motifs in natural products and bioactive molecules. Recently, biocatalytic cyclopropanations have emerged as a powerful approach to access enantioenriched cyclopropanes, complementing chemocatalytic approaches developed over the last several decades. Here, we report the development of a first biocatalytic strategy for cyclopropanation using ethyl α-diazopyruvate as a novel enzyme-compatible carbene precursor. Using myoglobin variant Mb(H64V,V68G) as the biocatalyst, this method afforded the efficient synthesis of α-cyclopropylpyruvates in high diastereomeric ratios and enantiomeric excess (up to 99% ee ). The ketoester moiety in the cyclopropane products can be used to synthesize diverse optically pure cyclopropane derivatives. Furthermore, the enzymatically obtained α-cyclopropylpyruvate products could be converted into enantiopure cyclobutenoates via a metal-free photochemical ring expansion without loss of optical activity. Competing Interests: Conflicts of interest There are no conflicts to declare. |
| Databáze: | MEDLINE |
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