Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction
The first example of a biocatalytic [2,3]-sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle-Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C–C bond forming transformation with high efficiency and p...
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ftpubmed:oai:pubmedcentral.nih.gov:5189672 2023-05-15T18:26:43+02:00 Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction Tyagi, Vikas Sreenilayam, Gopeekrishnan Bajaj, Priyanka Tinoco, Antonio Fasan, Rudi 2016-09-20 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189672/ http://www.ncbi.nlm.nih.gov/pubmed/27647732 https://doi.org/10.1002/anie.201607278 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189672/ http://www.ncbi.nlm.nih.gov/pubmed/27647732 http://dx.doi.org/10.1002/anie.201607278 Article Text 2016 ftpubmed https://doi.org/10.1002/anie.201607278 2017-10-22T00:02:54Z The first example of a biocatalytic [2,3]-sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle-Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C–C bond forming transformation with high efficiency and product conversions across a variety of sulfide substrates (i.e., aryl-, benzyl-, and alkyl-substituted allylic sulfides) and α-diazo esters. Moreover, the scope of this myoglobin-mediated transformation could be extended to the conversion of propargylic sulfides to give substituted allenes. Active site mutations proved effective toward enhancing the catalytic efficiency of the hemoprotein in these reactions as well as modulating its enantioselectivity, resulting in the identification of a myoglobin variant, Mb(L29S, H64V, V68F), capable of mediating asymmetric Doyle-Kirmse reactions with an enantiomeric excess up to 71%. This work extends the toolbox of currently available biocatalytic strategies for realizing the asymmetric formation of carbon–carbon bonds. Text Sperm whale PubMed Central (PMC) Doyle ENVELOPE(-65.300,-65.300,-66.000,-66.000) Angewandte Chemie International Edition 55 43 13562 13566 |
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Article Tyagi, Vikas Sreenilayam, Gopeekrishnan Bajaj, Priyanka Tinoco, Antonio Fasan, Rudi Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
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The first example of a biocatalytic [2,3]-sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle-Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C–C bond forming transformation with high efficiency and product conversions across a variety of sulfide substrates (i.e., aryl-, benzyl-, and alkyl-substituted allylic sulfides) and α-diazo esters. Moreover, the scope of this myoglobin-mediated transformation could be extended to the conversion of propargylic sulfides to give substituted allenes. Active site mutations proved effective toward enhancing the catalytic efficiency of the hemoprotein in these reactions as well as modulating its enantioselectivity, resulting in the identification of a myoglobin variant, Mb(L29S, H64V, V68F), capable of mediating asymmetric Doyle-Kirmse reactions with an enantiomeric excess up to 71%. This work extends the toolbox of currently available biocatalytic strategies for realizing the asymmetric formation of carbon–carbon bonds. |
format |
Text |
author |
Tyagi, Vikas Sreenilayam, Gopeekrishnan Bajaj, Priyanka Tinoco, Antonio Fasan, Rudi |
author_facet |
Tyagi, Vikas Sreenilayam, Gopeekrishnan Bajaj, Priyanka Tinoco, Antonio Fasan, Rudi |
author_sort |
Tyagi, Vikas |
title |
Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
title_short |
Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
title_full |
Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
title_fullStr |
Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
title_full_unstemmed |
Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction |
title_sort |
biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed doyle-kirmse reaction |
publishDate |
2016 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189672/ http://www.ncbi.nlm.nih.gov/pubmed/27647732 https://doi.org/10.1002/anie.201607278 |
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ENVELOPE(-65.300,-65.300,-66.000,-66.000) |
geographic |
Doyle |
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Doyle |
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Sperm whale |
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Sperm whale |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189672/ http://www.ncbi.nlm.nih.gov/pubmed/27647732 http://dx.doi.org/10.1002/anie.201607278 |
op_doi |
https://doi.org/10.1002/anie.201607278 |
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Angewandte Chemie International Edition |
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55 |
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43 |
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13562 |
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13566 |
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1766208697581699072 |