Synthesis, Chiral Resolution and Enantiomers Absolute Configuration of 4-Nitropropranolol and 7-Nitropropranolol

Sparaco, Rosa; Scognamiglio, Antonia; Corvino, Angela; Caliendo, Giuseppe; Fiorino, Ferdinando; Magli, Elisa; Perissutti, Elisa; Santagada, Vincenzo; Severino, Beatrice; Luciano, Paolo; Casertano, Marcello; Aiello, Anna; Nucci, Gilberto De; Frecentese, Francesco

doi:10.3390/molecules28010057

Cited by 5 publications

(10 citation statements)

References 21 publications

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“…The absolute configuration of 1 was assigned as (5R,1′R) by a single-crystal X-ray diffraction experiment using Cu-Kα radiation [16] were observed in the same CDCl3 solvent, which suggested that 2 could be a 5-epimer of 1 (Table 1). The absolute configuration of the secondary hydroxylated carbon (C-1′) was determined using a modified Mosher's method [17][18][19][20]. The chemical shifts for H-2′, H-4, and H-7 of 1a and 1b were measured as δH 1.49, 4.94, 2.38 for 1a, and δH 1.44, 4.96, 2.49 for 1b, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Compound 2 shared the same planar structure as 1 and was further identified by 2D NMR spectra, including 1 1). The absolute configuration of the secondary hydroxylated carbon (C-1′) wa determined using a modified Mosher's method [17][18][19][20]. The chemical shifts for H-2′, H-4 and H-7 of 1a and 1b were measured as δH 1.49, 4.94, 2.38 for 1a, and δH 1.44, 4.96, 2.49 fo 1b, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The minor chemical shift variation in C-4 (δC 25.6, δH 2.62, 1.98 for 1; δC 25.5, δH 2.68, 1.93 for 2), C-5 (δC 93.6 for 1; δC 94.0 for 2), C-1′ (δC 65.4, δH 4.22 for 1; δC 65.8, δH 4.19 for 2), and C-2′ (δC 16.3, δH 1.13 for 1; δC 16.3, δH 1.31 for 2)were observed in the same CDCl3 solvent, which suggested that 2 could be a 5-epimer of 1 (Table1). The absolute configuration of the secondary hydroxylated carbon (C-1′) was determined using a modified Mosher's method[17][18][19][20]. The chemical shifts for H-2′, H-4, and H-7 of 1a and 1b were measured as δH 1.49, 4.94, 2.38 for 1a, and δH 1.44, 4.96, 2.49 for 1b, respectively.…”

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confidence: 99%

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Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

Chen,

Guo

et al. 2024

Marine Drugs

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Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (−)-nigrosporine C (−)-3, together with eight known compounds (4–11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1–3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher’s method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 μmol/L and without cytotoxicity in a concentration of 100.0 μmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 μmol/L.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

Chen,

Guo

et al. 2024

Marine Drugs

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“…Due to its electron-withdrawing nature, the nitrogroup may provide functional diversity (Kamisaki et al, 1998). ()-4-Nitro-propranolol and ()-7-nitro-propranolol have been synthetized as racemic mixtures, and the enantiomers purified following chiral high-pressure liquid chromatography (Sparaco et al, 2022). Here, it was investigated the effects of (±)-propranolol, ()-4-NO2-propranolol, and ()-7-NO2propranolol and their respective (R)-and (S)-enantiomers on both the spontaneous atrial rate and the positive chronotropic effects induced by noradrenaline, adrenaline, and 6-ND.…”

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confidence: 99%

The effect of (±)-4-NO 2 -propranolol, (±)-7-NO 2 -propranolol, and (±)- propranolol on the rat isolated right atrium

Oliveira,

Cardoso,

Britto-Júnior

et al. 2024

Preprint

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6-Nitrodopamine (6-ND) is released from rat isolated atria and has positive chronotropic action, which is selectively blocked by β1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranolol, were investigated in the rat isolated right atrium. The atrium was mounted in gassed (95%O2:5%CO2), heated (37°C) glass chambers, containing Krebs-Henseleit’s solution. Tissues were allowed to equilibrate under a resting tension of 10mN for 1 hour, and the isometric tension was registered using a PowerLab system. (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol, caused concentration-dependent falls in the spontaneous atrial frequency (pEC50 were 4.80 ± 0.10, 4.64 ± 0.10, and 4.95 ± 0.10, respectively). Noradrenaline (1nM–30µM), and adrenaline (1nM–100µM), caused concentration-dependent increases in atrial rate. The calculated pA2 values for (±)-propranolol, (±)-4-NO2-propranolol, and (±)-7-NO2-propranol obtained for noradrenaline-induced positive chronotropic effects were 8.21 ± 0.35, 6.41 ± 0.21, and 8.35 ± 0.35, respectively. The positive chronotropic effect induced by 6-ND (10pM) was blocked by (±)-propranolol (1µM), and (±)-4-NO2-propranolol (30nM). (±)-7-NO2-propranol (1µM) had no effect on 6-ND (10pM)-induced increases in atrial rate. The pEC50 of (±)-propranolol, (±)-4-NO2-propranolol and (±)-7-NO2-propranolol were significantly shifted to the right in L-NAME treated atria. The discrepancy between pA2 values of (±)-propranolol and its respective pEC50 indicates that the falls in atrial rate induced by (±)-propranolol should not be attributed to b-adrenergic antagonism. The finding that (±)-4-NO2-propranolol causes falls in spontaneous atrial rate only in concentrations that affect 6-ND positive chronotropic effect, confirms the role of this catecholamine as endogenous modulator of heart chronotropism.

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“…Due to its electron-withdrawing nature, the nitrogroup may provide functional diversity. 4-nitro-propranolol and 7-nitro-propranolol have been synthetized as racemic mixtures, and the enantiomers purified following chiral high pressure liquid chromatography method (Sparaco et al, 2022). Here, it was investigated the effect of both propranolol analogues, and their respective enantiomers (S)-(+)-4-NO2-propranolol, (R)-(-)-4-NO2-propranolol, (S)-(+)-7-NO2-propranolol and (R)-(-)-7-NO2-propranolol), on the rat isolated right atrium basal rate and on the positive chronotropic effects induced by 6-ND, dopamine, noradrenaline, and adrenaline.…”

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confidence: 99%

4-Nitro-propranolol selectively inhibits the positive chronotropic effect induced by 6-nitrodopamine in the rat isolated right atrium

Oliveira,

Cardoso,

Britto-Júnior

et al. 2023

Preprint

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6-Nitrodopamine (6-ND) is released from isolated atria of rabbit, rat and mice and has significant positive chronotropic action. The positive chronotropic effect induced by 6-ND is selectively blocked by β1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of propranolol, 4-NO2-propranolol and 7-NO2-propranolol were investigated in the rat isolated right atrium. The right atrium was mounted between two metal hooks in 10-mL custom designed glass chambers containing Krebs-Henseleit’s solution, continuously gassed (95%O2:5%CO2) and heated (37°C). Tissues were allowed to equilibrate under a resting tension of 10 mN for one hour, and the isometric tension was registered using a PowerLab system. 4-NO2-propranol was more potent than propranolol as a negative chronotropic agent. At 30 nM, 4-NO2-propranolol did not affect the chronotropic effect of dopamine, noradrenaline, and adrenaline. The S-isomer of 4- NO2-propranolol, but not the R-isomer, was active. Propranolol induced fall in atrial rate at concentrations higher than those required to block the chronotropic effects of dopamine, noradrenaline and adrenaline, but enough to block the 6-ND effect. 7-NO2-propranolol was only active at very high concentration, and the effect was not stereoselective. The negative chronotropic effects induced by 4-NO2-propranolol (100 nM) and propranolol (300 nM) were not observed in L-NAME treated atria, whereas that induced by 7-NO2-propranolol (10 mM) was unaffected. The potent and selective inhibition observed with (±)-4-NO2-propranolol reinforces the concept that 6-ND is a major mediator of heart chronotropism and the main target of the so-called b-blockers.

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Synthesis, Chiral Resolution and Enantiomers Absolute Configuration of 4-Nitropropranolol and 7-Nitropropranolol

Cited by 5 publications

References 21 publications

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024

The effect of (±)-4-NO 2 -propranolol, (±)-7-NO 2 -propranolol, and (±)- propranolol on the rat isolated right atrium

4-Nitro-propranolol selectively inhibits the positive chronotropic effect induced by 6-nitrodopamine in the rat isolated right atrium

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