Determination of the position of the N-O function in substituted pyrazine N-oxides by chemometric analysis of carbon-13 nuclear magnetic resonance data

Butler, Matías; Cabrera, Gabriela M.

doi:10.1016/j.molstruc.2013.03.058

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…Once we established the biocatalysis system for preparative scale ArN→O synthesis, we aimed to challenge m CPBA‐based oxidation as this is the most typical chemical reagent used for the laboratory‐scale synthesis of ArN→O (Vörös et al ., 2014). For some pyrazine derivatives, N ‐oxidation with m CPBA results in unwelcome side reactions including the formation of di‐ N ‐oxides or isomeric mono‐ N ‐oxides as in the case of asymmetric pyrazines bearing various alkyl substituents (Sato, 1985; Butler and Cabrera, 2013). However, di‐ N ‐oxide formation from compounds 2a and 6a was easily handled in the case of a biocatalytic method (Fig.…”

Section: Resultsmentioning

confidence: 99%

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

Petkevičius

Vaitekūnas

Gasparavičiūtė

et al. 2021

Microbial Biotechnology

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Here, we present an improved whole-cell biocatalysis system for the synthesis of heteroaromatic N-oxides based on the production of a soluble di-iron monooxygenase PmlABCDEF in Pseudomonas sp. MIL9 and Pseudomonas putida KT2440. The presented biocatalysis system performs under environmentally benign conditions, features a straightforward and inexpensive procedure and possesses a high substrate conversion and product yield. The capacity of gram-scale production was reached in the simple shake-flask cultivation. The template substrates (pyridine, pyrazine, 2aminopyrimidine) have been converted into pyridine-1-oxide, pyrazine-1-oxide and 2-aminopyrimidine-1oxide in product titres of 18.0, 19.1 and 18.3 g l -1 , respectively. To our knowledge, this is the highest reported productivity of aromatic N-oxides using biocatalysis methods. Moreover, comparing to the chemical method of aromatic N-oxides synthesis based on meta-chloroperoxybenzoic acid, the developed approach is applicable for a regioselective oxidation that is an additional advantageous option in the preparation of the anticipated N-oxides.

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Section: Resultsmentioning

confidence: 99%

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

Petkevičius

Vaitekūnas

Gasparavičiūtė

et al. 2021

Microbial Biotechnology

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“…Synthesis and spectroscopic characterization of the compounds under study (Fig. ) have been previously reported . LCMS grade methanol and water were purchased from Carlo Erba (Milan, Italy).…”

Section: Methodsmentioning

confidence: 99%

“…1) have been previously reported. [21] LCMS grade methanol and water were purchased from Carlo Erba (Milan, Italy). The analyte solutions (1a-11a; 1b-11b) were prepared using methanol, each at a concentration of 10 mM.…”

Section: Experimental Chemicalsmentioning

confidence: 99%

A mass spectrometry-based method for differentiation of positional isomers of monosubstituted pyrazineN-oxides using metal ion complexes

Butler

Cabrera

2015

J. Mass Spectrom.

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A series of 11 pairs of substituted pyrazine N-oxides, differing in the substituent position, were examined using electrospray ionization mass spectrometry (ESI-MS) in order to use spectra to assess the differentiation of positional isomers. For each compound, mass spectra were recorded with three different metal cations, namely calcium (II), copper (II) and aluminum (III), with characterization of the observed peaks. Differentiation between regioisomeric N-oxides has been achieved by comparison of the identity and relative intensities of the peaks originating from the adduct ions formed with the metal ions. Principal component analysis (PCA) has been employed to assist in the interpretation of the results obtained with each metal ion, exploring possible trends according to the nature and position of the substituent in the pyrazine N-oxide.

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“…The resonance of the methine proton for the other analogues showed the effects of quadrupole broadening due to interaction with the nitrogen atom. This effect usually reduces the accuracy in the measurement of the spin-spin coupling constants of the protons in direct proximity to the nitrogen [32]. Their proton and carbon-13 NMR spectra revealed the presence of an increased number of aromatic proton and carbon signals consistent with the assigned structures.…”

Section: Chemistrymentioning

confidence: 99%

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

Magwaza,

More,

Gildenhuys

et al. 2023

Antioxidants

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Series of the 6-bromo/iodo substituted 2-aryl-4-methyl-1,2-dihydroquinazoline-3-oxides and their mixed 6,8-dihalogenated (Br/I and I/Br) derivatives were evaluated for inhibitory properties against α-glucosidase and/or α-amylase activities and for cytotoxicity against breast (MCF-7) and lung (A549) cancer cell lines. The 6-bromo-2-phenyl substituted 3a and its corresponding 6-bromo-8-iodo-2-phenyl-substituted derivative 3i exhibited dual activity against α-glucosidase (IC50 = 1.08 ± 0.02 μM and 1.01 ± 0.05 μM, respectively) and α-amylase (IC50 = 5.33 ± 0.01 μM and 1.18 ± 0.06 μM, respectively) compared to acarbose (IC50 = 4.40 ± 0.05 μM and 2.92 ± 0.02 μM, respectively). The 6-iodo-2-(4-fluorophenyl)-substituted derivative 3f, on the other hand, exhibited strong activity against α-amylase and significant inhibitory effect against α-glucosidase with IC50 values of 0.64 ± 0.01 μM and 9.27 ± 0.02 μM, respectively. Compounds 3c, 3l and 3p exhibited the highest activity against α-glucosidase with IC50 values of 1.04 ± 0.03, 0.92 ± 0.01 and 0.78 ± 0.05 μM, respectively. Moderate cytotoxicity against the MCF-7 and A549 cell lines was observed for these compounds compared to the anticancer drugs doxorubicin (IC50 = 0.25 ± 0.05 μM and 0.36 ± 0.07 μM, respectively) and gefitinib (IC50 = 0.19 ± 0.04 μM and 0.25 ± 0.03 μM, respectively), and their IC50 values are in the range of 10.38 ± 0.08–25.48 ± 0.08 μM and 11.39 ± 0.12–20.00 ± 0.05 μM, respectively. The test compounds generally exhibited moderate to strong antioxidant capabilities, as demonstrated via robust free radical scavenging activity assays, viz., DPPH and NO. The potential of selected derivatives to inhibit superoxide dismutase (SOD) was also investigated via enzymatic assay in vitro. Molecular docking revealed the N-O moiety as essential to facilitate electrostatic interactions of the test compounds with the protein residues in the active site of α-glucosidase and α-amylase. The presence of bromine and/or iodine atoms resulted in increased hydrophobic (alkyl and/or π-alkyl) interactions and therefore increased inhibitory effect against both enzymes.

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Determination of the position of the N-O function in substituted pyrazine N-oxides by chemometric analysis of carbon-13 nuclear magnetic resonance data

Cited by 8 publications

References 46 publications

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

An efficient and regioselective biocatalytic synthesis of aromatic N‐oxides by using a soluble di‐iron monooxygenase PmlABCDEF produced in the Pseudomonas species

A mass spectrometry-based method for differentiation of positional isomers of monosubstituted pyrazineN-oxides using metal ion complexes

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

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