Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization

Bioinspired, synthetic porphyrin complexes are important catalysts in organic synthesis and play a pivotal role in efficient carbene transfer reactions. The advances in this research area stimulated recent, “chemo‐inspired” developments in biocatalysis. Today, both synthetic iron complexes and enzymes play an important role to conduct carbene transfer reactions. The advances and potential developments in both research areas are discussed in this concept article.

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“…These results were achieved by directed evolution starting from 13 TON and yielding up to 2,020 TON as well as 96.7 : 3.3 e.r. (Scheme c) …”

Section: From X‐h Towards Modern C‐h Functionalization Reactionsmentioning

confidence: 99%

Iron‐porphyrin Catalyzed Carbene Transfer Reactions – an Evolution from Biomimetic Catalysis towards Chemistry‐inspired Non‐natural Reactivities of Enzymes

Weissenborn

Koenigs

2020

ChemCatChem

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“…Metal carbene formation from diazo precursors was found to be the rate‐determining step in many viable reactions catalyzed by iron porphyrins and other metal catalysts,– although exceptions were reported recently . The first quantum chemical study of IPC formation was reported in 2015 for formal Fe II systems .…”

Section: Heme Carbenesmentioning

confidence: 99%

Computational Investigations of Heme Carbenes and Heme Carbene Transfer Reactions

Zhang

2019

Chemistry A European J

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Engineered heme proteins and biomimetic iron porphyrins have been found to possess excellent catalytic properties for numerous carbene transfer reactions. Computational studies, including the use of DFT calculations and molecular dynamics simulations, have been employed to help understand some important mechanistic aspects of heme carbene transfer reactions. This review summarizes advances in the computational results published in the following two areas: 1) the electronic and geometric structures of heme carbenes; spectroscopic properties; and effects of carbene substituent, porphyrin substituent, axial ligand, and spin state on heme carbene formation; and 2) mechanisms of heme carbenoid X−H (X=C, Si, B, N, S) insertions and cyclopropanation, including effects of heme carbene structural components and protein environment, as well as oxidation state and spin state. A brief outlook of future development is also addressed.

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“…[1] At the same time,i tc an be considered as one of the biggest challenges as well. [2] While significant efforts have been dedicated to CYPs, [3] 2-oxoglutaratedependent dioxygenases have gained rather moderate attention thus far. [1] In contrast to these endeavors,nature provides selectivity for C À Ha ctivation through the enzymesa ctive site,w hich properly aligns the substrate(s) towards the active center.The most prominent representatives are cytochrome P450 monooxygenases (CYPs), which activate the CÀHb ond at an iron heme center with oxygen as aco-substrate.…”

mentioning

confidence: 99%

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

et al. 2019

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Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy‐, epi ‐, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2‐oxoglutarate‐dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non‐natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C−C bond formation by C−H activation or hydroxylation at the benzylic position prone to ring closure.

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Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization

Cited by 275 publications

References 30 publications

Iron‐porphyrin Catalyzed Carbene Transfer Reactions – an Evolution from Biomimetic Catalysis towards Chemistry‐inspired Non‐natural Reactivities of Enzymes

Iron‐porphyrin Catalyzed Carbene Transfer Reactions – an Evolution from Biomimetic Catalysis towards Chemistry‐inspired Non‐natural Reactivities of Enzymes

Computational Investigations of Heme Carbenes and Heme Carbene Transfer Reactions

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

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