Synthesis of Enantioenriched Sulfoxides by an Oxidation‐Reduction Enzymatic Cascade

Wang, Peipei; Han, Xiaofeng; Liu, Xinqi; Lin, Richen; Chen, Yongzheng; Sun, Zhoutong; Zhang, Wuyuan

doi:10.1002/chem.202201997

Cited by 8 publications

(1 citation statement)

References 36 publications

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“…Sulfur-containing compounds play a crucial role in diverse applications, serving as key intermediates for synthesizing pharmaceuticals, − agrochemicals, − and polymers. , Natural sulfur-containing products from plants like onion and garlic exhibit notable biological activities. − Researchers aim to develop efficient methods for generating C–S bonds; the focus is on environmentally friendly, cost-effective approaches to promote sustainable and selective C–S bond formation. − …”

Section: Introductionmentioning

confidence: 99%

Mechanistic Insights into the Selective C–S Bond Formation by P450 TleB

Gao,

Fan,

et al. 2024

ACS Catal.

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The P450 monooxygenase TleB (CYP107E48) catalyzes intramolecular C–S bond formation in a thiol-containing substrate, yielding two sulfur-containing indolactam derivatives (P1 and P2). However, the key sites influencing TleB’s product selectivity and the molecular mechanisms underlying the selective C–S bond formation are not fully understood. To address this, we created an artificial self-sufficient P450, TleB-CYP116B46, by fusing TleB with the reductase domain of CYP116B46. Structure-guided engineering of TleB-CYP116B46 generates variant L85G with 99% selectivity for P1 and variant I282L/Q387L/I234F with 95% selectivity for P2. Exploring TleB homologues and generating corresponding mutants elucidate the identified sites’ crucial role in product selectivity. Computational studies suggest a diradical mechanism for C–S bond formation for both P1 and P2 products. Intriguingly, we found that the substrate radical could undergo conformational changes in both the S–H and indole groups. The L85G variant facilitates the conformational switch of the indole radical group, thereby leading to the selective C–S bond formation for the P1 product. By contrast, the I282L/Q387L/I234F variant barricades the conformational switch of the indole radical group, affording the P2 product. Our simulations highlight that the protein environment can dictate the dynamics and positioning of the substrate radical, thereby leading to the selective C–S bond formation in P450s.

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Section: Introductionmentioning

confidence: 99%

Mechanistic Insights into the Selective C–S Bond Formation by P450 TleB

Gao,

Fan,

et al. 2024

ACS Catal.

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Chemoenzymatic Synthesis of Sterically Hindered Biaryls by Suzuki Coupling and Vanadium Chloroperoxidase Catalyzed Halogenations

Huang

Sun

et al. 2022

ChemBioChem

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Halogenated biaryls are vital structural skeletons in bioactive products. In this study, an effective chemoenzymatic halogenation by vanadium-dependent chloroperoxidase from Camponotus inaequalis (CiVCPO) enabled the transformation of freely rotating biaryl bonds to sterically hindered axis. The yields were up to 84 % for the tribrominated biaryl products and up to 65 % when isolated. Furthermore, a one-pot, two-step chemoenzy-matic strategy by incorporating transition metal catalyzed Suzuki coupling and the chemoenzymatic halogenation in aqueous phase were described. This strategy demonstrates a simplified one-pot reaction sequence with organometallic and biocatalytic procedures under economical and environmentally beneficial conditions that may inspire further research on synthesis of sterically hindered biaryls.

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Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

Bierbaumer,

Glueck,

Winkler

et al. 2024

ChemCatChem

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The synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom‐efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme‐catalyzed reduction of rac‐sulfoxides was combined with a stereo‐unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step‐wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99% ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.

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Synthesis of Enantioenriched Sulfoxides by an Oxidation‐Reduction Enzymatic Cascade

Cited by 8 publications

References 36 publications

Mechanistic Insights into the Selective C–S Bond Formation by P450 TleB

Mechanistic Insights into the Selective C–S Bond Formation by P450 TleB

Chemoenzymatic Synthesis of Sterically Hindered Biaryls by Suzuki Coupling and Vanadium Chloroperoxidase Catalyzed Halogenations

Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

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