Enzymatic Lactone-Carbene C–H Insertion to Build Contiguous Chiral Centers

Zhou, Andrew Z.; Chen, Kai; Arnold, Frances H.

doi:10.1021/acscatal.0c01349

Cited by 46 publications

(56 citation statements)

References 72 publications

(26 reference statements)

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“…79,80 Additionally, hemoproteins have been engineered for insertion of carbenes into N-H, 81,82 S-H, 68,83 Si-H, 84 and B-H bonds. [85][86][87] These advancements recently culminated in P411 enzymes proficient at inserting carbenes into C(sp 3 )-H bonds, [88][89][90] a reaction with enormous potential to transform the way we construct C-C bonds.…”

Section: New Hemoprotein Activities Emergementioning

confidence: 99%

Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

2020

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Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O 2 . Iron-dependent oxygenases exploit this earthabundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C-H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward.

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Section: New Hemoprotein Activities Emergementioning

confidence: 99%

Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases

2020

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“…Afterward, Arnold and colleagues have used cytochrome P411‐enzymes assembly, developed by the mutation of cysteine with serine at the axial position of cytochrome‐P450, to catalyze the lactone‐carbene insertion into primary and secondary α‐amino C−H bonds (Scheme 59). [74] This enzymatic reaction produced the analogues of sesquiterpene lactone amino derivatives in a stereodivergent manner. A number of variants were compatible to perform lactone‐carbene insertion into N,N‐dialkyl aniline derivatives with different activity and selectivity.…”

Section: Enzyme Based Catalystmentioning

confidence: 99%

Recent Advances in Iron‐Catalyzed Chemical and Enzymatic Carbene‐Transfer Reactions

Kaur

Tyagi

2021

Adv Synth Catal

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The use of diazo compounds in the transition‐metal‐catalyzed coupling reactions to form C−C and C−X (X=O, S, N, Si, P etc.) bonds have been a well established approach in organic synthesis. In this context, various transition metals such as Pd, Cu, Rh, Ni, Co, Fe, Ir etc. have proved useful to generate a metal‐carbene intermediate which subsequently undergoes carbene transfer or insertion to form C−C, C−Si or C‐heteroatom bonds. However, the use of most abundant, cheaper and environmentally benign metal such as iron to catalyze carbene‐transfer reactions has attracted considerable attention in the last few years. Iron is the second most abundant transition metal in nature and also an integral part of various biological systems which make it highly valuable to use as a catalyst in organic chemistry. This review summarizes the efforts made after 2013 in the area of iron‐catalyzed chemical and enzymatic carbene‐transfer reactions using diazo compounds as carbene precursor.

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“…Durch die Einführung dieser funktionellen Gruppe waren zahlreiche Derivate des Sequiterpenlactonamins (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74) in hohen Enantio-und Diastereoselektivitäten zugänglich. [82] Kürzlich wurde über die Konstruktion von P411-Enzymen für die C(sp 3 )-H-Aminierung berichtet. Die hochgradig regiound chemoselektive primäre Amininierung war in allylischen und benzylischen Positionen mçglich (75-78, Abbildung 12 ad).…”

Section: Nicht-natürliche Oxyfunktionalisierungenunclassified