Repurposing myoglobin into a carbene transferase for a [2,3]-sigmatropic Sommelet-Hauser rearrangement - Archive ouverte HAL
Journal Articles Journal of Inorganic Biochemistry Year : 2024

Repurposing myoglobin into a carbene transferase for a [2,3]-sigmatropic Sommelet-Hauser rearrangement

Abstract

New-to-Nature biocatalysis has emerged as a promising tool in organic synthesis thanks to progress in protein engineering. Notably, hemeproteins have been evolved into robust catalysts for carbene and nitrene transfers and related sigmatropic rearrangements. In this work, we report the first example of a [2,3]-sigmatropic Sommelet-Hauser rearrangement initiated by a carbene transfer of the sperm whale myoglobin mutant L29S,H64V,V68F that was previously reported to catalyze the mechanistically similar [2,3]-sigmatropic Doyle-Kirmse rearrangement. This repurposed heme enzyme catalyzes the Sommelet-Hauser rearrangement between ethyl diazoacetate and benzyl thioethers bearing strong electron-withdrawing substituents with good yields and enantiomeric excess. Optimized catalytic conditions in the absence of any reductant led to an increased asymmetric induction with up to 59% enantiomeric excess. This myoglobin mutant is therefore one of the few catalysts for the asymmetric Sommelet-Hauser rearrangement. This work broadens the scope of abiological reactions catalyzed by iron-carbene transferases with a new example of asymmetric sigmatropic rearrangement.
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Year Month Jours
Avant la publication
Friday, January 31, 2025
Embargoed file
Friday, January 31, 2025
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Dates and versions

hal-04668325 , version 1 (06-08-2024)

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Manon Pujol, Lison Degeilh, Thibault Sauty de Chalon, Marius Réglier, A. Jalila Simaan, et al.. Repurposing myoglobin into a carbene transferase for a [2,3]-sigmatropic Sommelet-Hauser rearrangement. Journal of Inorganic Biochemistry, 2024, 260, pp.112688. ⟨10.1016/j.jinorgbio.2024.112688⟩. ⟨hal-04668325⟩
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