An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones
Abstract Abiological enzymes offers new opportunities for sustainable chemistry. Herein, we report the development of biological catalysts derived from sperm whale myoglobin that exploit a carbene transfer mechanism for the asymmetric synthesis of cyclopropane‐fused‐δ‐lactones, which are key structu...
Published in: | Angewandte Chemie |
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Online Access: | http://dx.doi.org/10.1002/ange.202007953 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.202007953 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/ange.202007953 |
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crwiley:10.1002/ange.202007953 2024-06-02T08:14:53+00:00 An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones Ren, Xinkun Liu, Ningyu Chandgude, Ajay L. Fasan, Rudi National Institutes of Health National Science Foundation 2020 http://dx.doi.org/10.1002/ange.202007953 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.202007953 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/ange.202007953 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#am http://onlinelibrary.wiley.com/termsAndConditions#vor Angewandte Chemie volume 132, issue 48, page 21818-21823 ISSN 0044-8249 1521-3757 journal-article 2020 crwiley https://doi.org/10.1002/ange.202007953 2024-05-03T11:02:49Z Abstract Abiological enzymes offers new opportunities for sustainable chemistry. Herein, we report the development of biological catalysts derived from sperm whale myoglobin that exploit a carbene transfer mechanism for the asymmetric synthesis of cyclopropane‐fused‐δ‐lactones, which are key structural motifs found in many biologically active natural products. While hemin, wild‐type myoglobin, and other hemoproteins are unable to catalyze this reaction, the myoglobin scaffold could be remodeled by protein engineering to permit the intramolecular cyclopropanation of a broad spectrum of homoallylic diazoacetate substrates in high yields and with up to 99 % enantiomeric excess. Via an alternate evolutionary trajectory, a stereodivergent biocatalyst was also obtained for affording mirror‐image forms of the desired bicyclic products. In combination with whole‐cell transformations, the myoglobin‐based biocatalyst was used for the asymmetric construction of a cyclopropyl‐δ‐lactone scaffold at a gram scale, which could be further elaborated to furnish a variety of enantiopure trisubstituted cyclopropanes. Article in Journal/Newspaper Sperm whale Wiley Online Library Angewandte Chemie 132 48 21818 21823 |
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Wiley Online Library |
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English |
description |
Abstract Abiological enzymes offers new opportunities for sustainable chemistry. Herein, we report the development of biological catalysts derived from sperm whale myoglobin that exploit a carbene transfer mechanism for the asymmetric synthesis of cyclopropane‐fused‐δ‐lactones, which are key structural motifs found in many biologically active natural products. While hemin, wild‐type myoglobin, and other hemoproteins are unable to catalyze this reaction, the myoglobin scaffold could be remodeled by protein engineering to permit the intramolecular cyclopropanation of a broad spectrum of homoallylic diazoacetate substrates in high yields and with up to 99 % enantiomeric excess. Via an alternate evolutionary trajectory, a stereodivergent biocatalyst was also obtained for affording mirror‐image forms of the desired bicyclic products. In combination with whole‐cell transformations, the myoglobin‐based biocatalyst was used for the asymmetric construction of a cyclopropyl‐δ‐lactone scaffold at a gram scale, which could be further elaborated to furnish a variety of enantiopure trisubstituted cyclopropanes. |
author2 |
National Institutes of Health National Science Foundation |
format |
Article in Journal/Newspaper |
author |
Ren, Xinkun Liu, Ningyu Chandgude, Ajay L. Fasan, Rudi |
spellingShingle |
Ren, Xinkun Liu, Ningyu Chandgude, Ajay L. Fasan, Rudi An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
author_facet |
Ren, Xinkun Liu, Ningyu Chandgude, Ajay L. Fasan, Rudi |
author_sort |
Ren, Xinkun |
title |
An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
title_short |
An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
title_full |
An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
title_fullStr |
An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
title_full_unstemmed |
An Enzymatic Platform for the Highly Enantioselective and Stereodivergent Construction of Cyclopropyl‐δ‐lactones |
title_sort |
enzymatic platform for the highly enantioselective and stereodivergent construction of cyclopropyl‐δ‐lactones |
publisher |
Wiley |
publishDate |
2020 |
url |
http://dx.doi.org/10.1002/ange.202007953 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.202007953 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202007953 https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/ange.202007953 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_source |
Angewandte Chemie volume 132, issue 48, page 21818-21823 ISSN 0044-8249 1521-3757 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#am http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/ange.202007953 |
container_title |
Angewandte Chemie |
container_volume |
132 |
container_issue |
48 |
container_start_page |
21818 |
op_container_end_page |
21823 |
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1800738889131884544 |