Regioselective Aliphatic Carbon–Carbon Bond Cleavage by a Model System of Relevance to Iron-Containing Acireductone Dioxygenase

Allpress, Caleb J.; Grubel, Katarzyna; Szajna-Fuller, Ewa; Arif, Atta M.; Berreau, Lisa M.

doi:10.1021/ja3038189

Cited by 56 publications

(36 citation statements)

References 42 publications

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“…This led us to propose a mechanistic pathway in which the Fe II center had an enhanced ability to promote the hydration of a vicinyl triketone intermediate, leading to a differentiation in regioselectivity. [22] In the current system, in the absence of water, the Ni II center has a directing effect on the chemistry, which makes this model system particularly relevant to Ni II -ARD. In terms of the reaction pathway leading to carbon-carbon bond cleavage, we note that the lack of an observed tricarbonyl intermediate (benzoylglyoxal) does not explicitly rule out the involvement of such a species.…”

Section: Discussionmentioning

confidence: 92%

“…Notably, no evidence was found by GC-MS of a tricarbonyl-type intermediate (benzoylglyoxal) akin to that involved in reaction the reaction of complex 1 bearing the bulky acireductone 2-hydroxy-1,3-diphenylpropane-1,3-dione as ligand (Scheme 2). [22,23] In addition, no evidence was found for the formation of benzoylformic acid, which would be the expected product if only C(1)-C(2) cleavage (Fe-ARDЈ-type) reaction occurred. …”

Section: Organic Product Analysismentioning

confidence: 99%

“…[21,22] Upon exposure to O 2 , these synthetic complexes undergo dioxygenolytic carbon-carbon bond cleavage via an intermediate trione/hydroperoxide pair. [22,23] It was found that the regioselectivity of the reaction of 1 and 2 with O 2 was identical in dry solvent, consistent with the chelate hypothesis. However, in the presence of H 2 O a change in regioselectivity was observed in the reaction of 2, but not of 1, which suggests that the chelate hypothesis is not sufficient to explain the chemistry in these model systems.…”

Section: Introductionmentioning

confidence: 99%

“…However, in the presence of H 2 O a change in regioselectivity was observed in the reaction of 2, but not of 1, which suggests that the chelate hypothesis is not sufficient to explain the chemistry in these model systems. [22] We therefore proposed a new reaction pathway for 2 in which the ferrous center promotes hydration of the triketone intermediate, thereby facilitating the change in regioselectivity (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

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A Nickel‐Containing Model System of Acireductone Dioxygenases that Utilizes a C(1)‐H Acireductone Substrate

Allpress

Berreau

2014

Eur J Inorg Chem

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β‐Hydroxy‐α‐amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β‐hydroxy‐α‐amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one‐flask protocol. Enolization of (R,R)‐ or (S,S)‐pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L‐ or D‐threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55–98 %, and are readily transformed into β‐hydroxy‐α‐amino acids by mild hydrolysis or into 2‐amino‐1,3‐diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.

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Section: Discussionmentioning

confidence: 92%

Section: Organic Product Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Nickel‐Containing Model System of Acireductone Dioxygenases that Utilizes a C(1)‐H Acireductone Substrate

Allpress

Berreau

2014

Eur J Inorg Chem

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“…However, recent experiments and computational studies challenge this view and propose a new explanation. 69,72,73 We found that the two metals bind the substrate in the same way, exposing the same sites to the nucleophilic attack by O 2 (Figure 8) …”

Section: ■ Metal Replacement Can Also Reroutementioning

confidence: 82%

Mysteries of Metals in Metalloenzymes

et al. 2014

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Conspectus Natural metalloenzymes are often the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions. However, metalloenzymes are occasionally surprising in their selection of catalytic metals, and in their responses to metal substitution. Indeed, from the isolated standpoint of producing the best catalyst, a chemist designing from first-principles would likely choose a different metal. For example, some enzymes employ a redox active metal where a simple Lewis acid is needed. Such are several hydrolases. In other cases, substitution of a non-native metal leads to radical improvements in reactivity. For example, histone deacetylase 8 naturally operates with Zn2+ in the active site but becomes much more active with Fe2+. For β-lactamases, the replacement of the native Zn2+ with Ni2+ was suggested to lead to higher activity as predicted computationally. There are also intriguing cases, such as Fe2+- and Mn2+-dependent ribonucleotide reductases and W4+- and Mo4+-dependent DMSO reductases, where organisms manage to circumvent the scarcity of one metal (e.g., Fe2+) by creating protein structures that utilize another metal (e.g., Mn2+) for the catalysis of the same reaction. Naturally, even though both metal forms are active, one of the metals is preferred in every-day life, and the other metal variant remains dormant until an emergency strikes in the cell. These examples lead to certain questions. When are catalytic metals selected purely for electronic or structural reasons, implying that enzymatic catalysis is optimized to its maximum? When are metal selections a manifestation of competing evolutionary pressures, where choices are dictated not just by catalytic efficiency but also by other factors in the cell? In other words, how can enzymes be improved as catalysts merely through the use of common biological building blocks available to cells? Addressing these questions is highly relevant to the enzyme design community, where the goal is to prepare maximally efficient quasi-natural enzymes for the catalysis of reactions that interest humankind. Due to competing evolutionary pressures, many natural enzymes may not have evolved to be ideal catalysts and can be improved for the isolated purpose of catalysis in vitro when the competing factors are removed. The goal of this Account is not to cover all the possible stories but rather to highlight how variable enzymatic catalysis can be. We want to bring up possible factors affecting the evolution of enzyme structure, and the large- and intermediate-scale structural and electronic effects that metals can induce in the protein, and most importantly, the opportunities for optimization of these enzymes for catalysis in vitro.

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Bacterial CYP154C8 catalyzes carbon‐carbon bond cleavage in steroids

Dangi

2018

FEBS Letters

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Here, we report the first bacterial cytochrome P450, CYP154C8, that catalyzes the C–C bond cleavage reaction of steroids. A major change in product distribution is observed with CYP154C8, when the reactions are supported by NADPH and spinach redox partners ferredoxin and ferredoxin reductase, compared with previously reported reactions supported by NADH and redox partners containing putidaredoxin and putidaredoxin reductase. The NMR‐based structural elucidation of reaction products reveals 21‐hydroxyprednisone as the major product for prednisone, while the other product is identified as 1‐dehydroadrenosterone obtained due to C–C bond cleavage. A similar pattern of product formation is observed with cortisone, hydrocortisone, and prednisone. The reaction catalyzed by CYP154C8 in the presence of oxygen surrogates also prominently shows the formation of C–C bond cleavage products.

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Regioselective Aliphatic Carbon–Carbon Bond Cleavage by a Model System of Relevance to Iron-Containing Acireductone Dioxygenase

Cited by 56 publications

References 42 publications

A Nickel‐Containing Model System of Acireductone Dioxygenases that Utilizes a C(1)‐H Acireductone Substrate

A Nickel‐Containing Model System of Acireductone Dioxygenases that Utilizes a C(1)‐H Acireductone Substrate

Mysteries of Metals in Metalloenzymes

Bacterial CYP154C8 catalyzes carbon‐carbon bond cleavage in steroids

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