Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
| Autor: | Alexandra Binter, Peter Macheroux, Marina Toplak, Rolf Breinbauer, Karl Gruber, Kathrin Heckenbichler, Anna Katharina Schweiger, Lea A. Brandner |
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| Rok vydání: | 2018 |
| Předmět: |
Cyclopropanes
Double bond Stereochemistry Flavin Mononucleotide asymmetric synthesis 010402 general chemistry 01 natural sciences Catalysis Cofactor Residue (chemistry) Solanum lycopersicum enoate reductases Ene reaction chemistry.chemical_classification Aldehydes biology 010405 organic chemistry Chemistry Hydride Communication Enantioselective synthesis NADPH Dehydrogenase protein engineering General Chemistry Ketones Communications 0104 chemical sciences Biocatalysis Cyclization Electrophile C−C-bond formation biology.protein Oxidoreductases Oxidation-Reduction Bacillus subtilis |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| ISSN: | 1521-3773 |
| Popis: | Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β‐unsaturated compounds bearing an electron‐withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C−C bonds. α,β‐Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two‐electron‐reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single‐site replacement of a crucial Tyr residue with a non‐protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee. |
| Databáze: | OpenAIRE |
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