Enzymatic approaches to site-selective oxidation of quinoline and derivatives

Sustainable functionalization of renewable aromatics is a key step to supply our present needs for specialty chemicals and pursuing the transition to a circular, fossil-free economy. In the present work, three typically stable aromatic compounds, representative of products abundantly obtainable from biomass or recycling processes, were functionalized in one-pot oxidation reactions at room temperature, using H2O2 as a green oxidant and ethanol as a green solvent in the presence of a highly electron withdrawing iron porphyrin catalyst. The results show unusual initial epoxidation of the aromatic ring by the green catalytic system. The epoxides were isolated or evolved through rearrangement, ring opening by nucleophiles, and oxidation. Acridine was oxidized to mono- and di-oxides in the peripheral ring: 1:2-epoxy-1,2-dihydroacridine and anti-1:2,3:4-diepoxy-1,2,3,4-tetrahydroacridine, with TON of 285. o-Xylene was oxidized to 4-hydroxy-3,4-dimethylcyclohexa-2,5-dienone, an attractive building block for synthesis, and 3,4-dimethylphenol as an intermediate, with TON of 237. Quinoline was directly functionalized to 4-quinolone or 3-substituted-4-quinolones (3-ethoxy-4-quinolone or 3-hydroxy-4-quinolone) and corresponding hydroxy-tautomers, with TON of 61.

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“…The direct oxidation of quinoline has been studied to obtain its degradation [28] or site-selective oxidation using enzymatic catalysis [29].…”

Section: Introductionmentioning

confidence: 99%

Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine

2023

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“…N ‐heterocycles feature heavily in pharmaceutical compounds, and have been the target of biocatalytic oxygenations by various alternative systems. [ 30 , 31 , 32 , 33 ] The oxygenation of N ‐heterocycles, like pyridine derivatives 1 and 3 , were identified as reactions of interest (Scheme 1 A), and hence their oxygenation was explored using Aae UPO, in addition to a much wider array of N ‐heterocyclic systems including alkyl pyridines, bicyclic N ‐heterocycles and indoles (Scheme 1 B). The results show that, in contrast to cell‐free P450‐based systems, Aae UPO can be readily applied to the hundreds‐of‐milligrams scale synthesis of oxygenated N ‐heterocyclic intermediates, with remarkable promiscuity, when applied as an easy‐to‐use cell free lyophilized powder.…”

Section: Introductionmentioning

confidence: 99%

Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized Peroxygenase Catalyst

et al. 2022

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A lyophilized preparation of an unspecific peroxygenase variant from Agrocybe aegerita (rAaeU-PO-PaDa-I-H) is a highly effective catalyst for the oxygenation of a diverse range of N-heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ca. 100 mg scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N-heterocycles and indoles. H 2 O 2 is the only stoichiometric oxidant needed, without auxiliary electron transport proteins, which is key to the practicality of the method. Reaction outcomes can be altered depending on whether hydrogen peroxide was delivered by syringe pump or through in situ generation using an alcohol oxidase from Pichia pastoris (PpAOX) and methanol as a co-substrate. Good synthetic yields (up to 84 %), regioselectivity and enantioselectivity (up to 99 % ee) were observed in some cases, highlighting the promise of UPOs as practical, versatile and scalable oxygenation biocatalysts.

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“…This study is focused on exploring the oxygenation of N ‐heterocyclic compounds (Scheme 1). N ‐heterocycles feature heavily in pharmaceutical compounds, and have been the target of biocatalytic oxygenations by various alternative systems [30–33] . The oxygenation of N ‐heterocycles, like pyridine derivatives 1 and 3 , were identified as reactions of interest (Scheme 1A), and hence their oxygenation was explored using Aae UPO, in addition to a much wider array of N ‐heterocyclic systems including alkyl pyridines, bicyclic N ‐heterocycles and indoles (Scheme 1B).…”

Section: Introductionmentioning

confidence: 99%

“…N-heterocycles feature heavily in pharmaceutical compounds, and have been the target of biocatalytic oxygenations by various alternative systems. [30][31][32][33] The oxygenation of N-heterocycles, like pyridine derivatives 1 and 3, were identified as reactions of interest (Scheme 1A), and hence their oxygenation was explored using AaeUPO, in addition to a much wider array of N-heterocyclic systems including alkyl pyridines, bicyclic N-heterocycles and indoles (Scheme 1B). The results show that, in contrast to cell-free P450-based systems, AaeUPO can be readily applied to the hundreds-of-milligrams scale synthesis of oxygenated N-heterocyclic intermediates, with remarkable promiscuity, when applied as an easy-to-use cell free lyophilized powder.…”

Section: Introductionmentioning

confidence: 99%

Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized Peroxygenase Catalyst

et al. 2022

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Enzymatic approaches to site-selective oxidation of quinoline and derivatives

Abstract: Enzyme-mediated oxidation has been a green and efficient strategy for preparation of derivative chemicals from quinoline and its structural analogues. Herein, we report the progress made till date, in enzymatic...

Cited by 5 publications

References 108 publications

Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine

Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine

Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized Peroxygenase Catalyst

Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized Peroxygenase Catalyst

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