Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade

Martínez‐Montero, Lía; Tischler, Dirk; Süss, Philipp; Schallmey, Anett; Franssen, M.C.R.; Hollmann, Frank; Paul, Caroline E.

doi:10.1039/d1cy00855b

Cited by 21 publications

(17 citation statements)

References 65 publications

(96 reference statements)

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“…Moreover, regioisomers 3a and especially 6a were formed with high regioselectivity in the HHDHcatalysed step (Table 2). Thus, our StyAB + HHDH cascade for the synthesis of aliphatic 2,3azidoalcohols compares favourably, in terms of regioselectivity, with the recently published cascade for the synthesis of aryl aliphatic azidoalcohols [12]. Overall, the poor organic solvent tolerance of the used HHDHs, HheE and HheE5, turned out to be a main limiting factor regarding product yield in both cascades, but also enantioselectivity in cascade 1.…”

Section: Cascade Runsmentioning

confidence: 58%

“…The aim of this work was to expand the range of accessible enantiopure azidoalcohols through a combination of alkene epoxidation and subsequent epoxide azidolysis, as recently reported for the generation of styrene-based azidoalcohols [12]. Here, we have demonstrated that this strategy can be extended to linear non-terminal alkene substrates, giving access to a broader range of possible azidoalcohol products.…”

Section: Discussionmentioning

confidence: 73%

“…Moreover, regioisomers 3a and especially 6a were formed with high regioselectivity in the HHDH-catalysed step (Table 2). Thus, our StyAB + HHDH cascade for the synthesis of aliphatic 2,3-azidoalcohols compares favourably, in terms of regioselectivity, with the recently published cascade for the synthesis of aryl aliphatic azidoalcohols [12]. [a] Determined by GC-FID [b] Ratio of formed azidoalcohol regioisomers [see Table 3].…”

Section: Cascade Runsmentioning

confidence: 99%

“…In a recent example, Martínez-Montero et al reported a (chemo)-enzymatic cascade for the synthesis of aromatic αand β-azidoalcohols. They coupled a styrene monooxygenase from Sphingopyxis fribergensis Kp5.2 either with chemical epoxide azidolysis or a set of HHDHs to synthesise different isomers of styrene-based azidoalcohols with high enantiopurity [12].…”

Section: Introductionmentioning

confidence: 99%

“…monooxygenase from Sphingopyxis fribergensis Kp5.2 either with chemical epoxide azidolysis or a set of HHDHs to synthesise different isomers of styrene-based azidoalcohols with high enantiopurity [12].…”

Section: Introductionmentioning

confidence: 99%

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Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Calderini

Süss²,

Hollmann

et al. 2021

Catalysts

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Multi-step cascade reactions have gained increasing attention in the biocatalysis field in recent years. In particular, multi-enzymatic cascades can achieve high molecular complexity without workup of reaction intermediates thanks to the enzymes’ intrinsic selectivity; and where enzymes fall short, organo- or metal catalysts can further expand the range of possible synthetic routes. Here, we present two enantiocomplementary (chemo)-enzymatic cascades composed of either a styrene monooxygenase (StyAB) or the Shi epoxidation catalyst for enantioselective alkene epoxidation in the first step, coupled with a halohydrin dehalogenase (HHDH)-catalysed regioselective epoxide ring opening in the second step for the synthesis of chiral aliphatic non-terminal azidoalcohols. Through the controlled formation of two new stereocenters, corresponding azidoalcohol products could be obtained with high regioselectivity and excellent enantioselectivity (99% ee) in the StyAB-HHDH cascade, while product enantiomeric excesses in the Shi-HHDH cascade ranged between 56 and 61%.

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Section: Cascade Runsmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 73%

Section: Cascade Runsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Calderini

Süss²,

Hollmann

et al. 2021

Catalysts

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Expanding the Scope of Enantioselective Halohydrin Dehalogenases – Group B

et al. 2022

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Halohydrin dehalogenases (HHDHs) possess an unnatural activity of introducing functionalities such as N3, CN, NO2 etc., into a molecule through the ring‐opening reaction of epoxides. The enantioselectivity of HHDHs is substrate‐dependent and not always high enough for synthetic applications. B‐group of HHDHs has been neglected in the past, due to observed low enantioselectivity based on performance on a relatively limited number of substrates. Extensive screening of substrates on HheB2 from Mycobacterium sp. GP1 and HheB from Corynebacterium sp. N‐1074 was performed. Several highly enantioselective reactions were discovered (E>200), with HheB showing higher enantioselectivity and activity toward larger panel of substrates compared to HheB2. Enzymes HheB and HheB2 are highly homologous; they differ by only 4 residues. By using site‐directed mutagenesis, residues 120 and 125 were found to be responsible for higher enantioselectivity of HheB compared to HheB2. Computational analysis supported experiments and provided evidence that kinetic and thermodynamic parameters of reactions within HheB enzymes are crucial in determining the observed enantioselectivities. Due to remarkable activity and enantioselectivity, B‐group HHDHs emerged as a catalyst of choice for the synthesis of bulky tertiary alcohols, as shown in this work.

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Synthesis of Enantiopure Vicinal Halohydrins Using a Sequence of Haloperoxidase and Lipase

De Marchi,

Hilberath,

Zippilli

et al. 2024

Adv Synth Catal

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Vicinal halohydrins are key building blocks to produce bioactive molecules and drugs, especially if they can be obtained in enantiomerically pure form. In this study, we present a bi‐enzymatic sequence that allows to obtain vic‐halohydrins through a photochemoenzymatic olefin hydroxy halogenation followed by a lipase catalysed kinetic resolution. The absolute configuration of the resulting products was determined using Mosher’s method.

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Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade

Abstract: Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of...

Cited by 21 publications

References 65 publications

Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Expanding the Scope of Enantioselective Halohydrin Dehalogenases – Group B

Synthesis of Enantiopure Vicinal Halohydrins Using a Sequence of Haloperoxidase and Lipase

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