Chemistry - A European Journal
10.1002/chem.201702350
DOI: 10.1002/chem.201xxxxxx
7
7
-1
-1
CDCl
3
): 23.2, 41.1, 42.6, 112.1, 118.8, 128.4, 128.8, 139.3, 152.4; Se NMR
10 seconds of reaction by using 1.24 mM cm as the extinction coefficient for
PhSSPh. Values reported in Table 2 are means ± SD based on triplicates.
+
+
(76 MHz, CDCl
3
): 441; HRMS (TOF MS EI ) m/z calcd for C
9
H
10OSe [M] :
213.9897; found: 213.9896.
Computational Details. Computational studies of compounds 8-11 were
[
33]
2-Methyl-2,3-dihydrobenzo[b]selenophene-7-ol (9). 15a (450 mg, 1.98 mmol)
performed by using the Gaussian 09 suite of quantum chemical programs.
was subjected to the conditions for O-demethylation as described for the
preparation of compounds 10 and 11. Purification by column chromatography
using DCM as an eluent afforded the title compound as a colorless liquid which
The geometry optimizations were carried out at the M062X/aug-cc-pVDZ level
of theory and the frequencies were also calculated at the same level of theory.
Calculations were performed by using Gaussian09/d.01 suite of programs.
o
1
solidified in the freezer. Yield: 0.15 g (36%); mp 68-70 C; H NMR (400 MHz,
CDCl ): 1.59 (d, J = 6.8 Hz, 3H), 3.10 (dd, J = 6.0, 15.2 Hz, 1H), 3.46 (dd, J =
.8, 15.2 Hz, 1H), 4.20 (m, 1H), 4.55 (s, 1H), 6.62 (d, J = 8.0 Hz, 1H), 6.80 (d, J
3
6
=
Acknowledgements
1
3
7.6 Hz, 1H), 6.98 (t, J = 7.2 Hz, 1H); C NMR (100 MHz, CDCl
3
): 22.8, 42.4,
):
10OSe [M+H] : 213.9897; found:
77
4
3
2
7.8, 113.7, 118.2, 126.1, 126.7, 144.9, 152.6; Se NMR (76 MHz, CDCl
85; HRMS (TOF MS EI ) m/z calcd for C
13.9904.
3
+
+
Stiftelsen Å-Forsk (16-364) and Stiftelsen Olle Engkvist Byggmästare
9
H
(2016/159) are gratefully acknowledged for financial support. Prof. Ray J.
Butcher wishes to acknowledge the assistance of August Ridenour and
Professor C. Cahill at George Washington University for collecting the X-ray
data.
[
17]
2
-Methyl-2,3-dihydrobenzo[b]selenophene-5-ol (8). Dihydroselenophene 8
1 13
was prepared as reported in literature. The H and C NMR spectra were in
good agreement with literature and have been included in the Supporting
Information.
Keywords: chain-breaking antioxidants • phenols•
dihydrobenzoselenophenes • lipid peroxidation • co-antioxidants
X-ray Crystallographic Analysis. X-ray crystallographic studies of 11 were
carried out using graphite-monochromatized Mo Kα radiation (λ = 0.7107 Å).
The structure was solved by direct methods (SHELXS-2016) and refined by a
[
[
1]
2]
a) R. Brigelius-Flohé, Free Radic. Biol. Med. 2009, 46, 543-554; b) R.
Brigelius-Flohé, F. Galli, Mol. Nutr. Food Res. 2010, 54, 583-587.
2
full-matrix least-squares procedure on F for all reflections using SHELXL-2016
[
30]
software.
Hydrogen atoms were localized by geometrical means. A riding
a) G. W. Burton, K. U. Ingold, Acc. Chem. Res. 1986, 19, 194-201; b) E.
Niki, N. Noguchi, Acc. Chem. Res. 2004, 37, 45-51; c) D. Marquardt, J. A.
Williams, N. Kucerka, J. Atkinson, S. R. Wassall, J. Katsaras, T. A.
Harroun, J. Am. Chem. Soc. 2013, 135, 7523-753.
model was chosen for refinement. The isotropic thermal parameters of
hydrogen atoms were fixed at 1.5 times and 1.2 times U(eq) of the
3
2
corresponding carbon atoms for sp C-H and sp C-H bonds, respectively.
Crystallographic data for the structure reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre (CCDC) as
supplementary publications. CCDC 1538259 (for compound 11) contains the
supplementary crystallographic data for this paper. These data can be obtained
free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif
[3]
B. Halliwell, J. M. C. Gutteridge, Free Radicals in Biology and Medicine,
th
4
Ed., Oxford University Press, Oxford, 2007, p. 168.
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4]
a) E. Niki, A. Kawakami, Y. Yamamoto, Y. Kamiya, Bull. Chem. Soc. Jpn.
985, 58, 1971-1975; b) T. Doba, G. W. Burton, K. U. Ingold, Biochem.
1
Biophys. Acta 1985, 835, 298-303.
Crystal data for 11. C
9
H10OSe, Mr = 213.13, orthorhombic, space group P b c
o
a, a = 12.8266(9) Å, b = 10.2338(7) Å, c = 12.9340(9) Å, α = β = γ = 90 , V =
[5]
a) K. U. Ingold, D. A. Pratt, Chem. Rev. 2014, 114, 9022-9046; b) L.
Valgimigli, D. A. Pratt, Acc. Chem. Res. 2015, 48, 966-975.
3
3
1
697.8(2) Å , = 0.71073 Å, Z = 8, T = 296(2) K, ρcalcd = 1.668 Mg/m , GOF =
1
.022, R1 = 0.0262, wR2 = 0.0557 [I>2σ (I)]; R1 = 0.0441, wR2 = 0.0611 (all
[
6]
a) S. Kumar, H. Johansson, T. Kanda, L. Engman, T. Müller, H.
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Chem. 2010, 75, 716-725; b) H. Johansson, D. Shanks, L. Engman, R.
Amorati, G. F. Pedulli, L. Valgimigli, J. Org. Chem. 2010, 75, 7535-7541;
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data). Of the 15941 reflections that were collected, 2104 were unique (Rint
.0332).
=
0
HPLC Peroxidation Assay: The experimental setup for recording inhibition
times (Tinh and inhibited rates of peroxidation (Rinh during azo-initiated
peroxidation of linoleic acid in a two-phase system were recently described.
)
)
[
21]
Fresh linoleic acid was used as purchased. Values reported in Tables 1 and 3
for reactions performed in the presence of NAC are means ± SD based on
triplicates. As Rinh- and Tinh-values show slight variations depending on the
amount of linoleic acid hydroperoxide which is always present in commercial
samples as an impurity, and increases upon storage. In the pH-variation
experiments HCl or NaOH were added to the NAC-solution until a pH-meter
indicated pH = 2, 5 and 7. Buffer solutions were tried but they always caused
serious problems in the HPLC analysis of conjugated diene.
2
447-2457.
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[
[
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NAC Consumption Assay: The concentration of NAC in the aqueous phase of
Janzen, Y. Kotake, K. U. Ingold, J. Org. Chem. 1988, 53, 3739-3745.
the two-phase model system during ongoing peroxidation was determined by
[
31]
using the assay of Means, with slight modifications. After every 30 min during
the first 3 hours of peroxidation, 20 μL of the aqueous phase was withdrawn by
syringe and injected into a UV cuvette. Then, 1 mL of a 0.25 M solution of
Aldrithiol-4 in water/DMF (49:1) was added. The concentration of pyridin-4-thiol
11] D. Shanks, R. Amorati, M. G. Fumo, G. F. Pedulli, L. Valgimigli, L.
Engman, J. Org. Chem. 2006, 71, 1033-1038.
[12] S. Menichetti, R. Amorati, M. G. Bartolozzi, G. F. Pedulli, A. Salvini, C.
was determined spectrophotometrically at 324 nm in comparison with
a
Viglianisi, Eur. J. Org. Chem. 2010, 2218-2225.
standard curve. The rate of NAC-consumption was calculated by least-square
methods from time/concentration plots. Values reported in Table 2 are means ±
SD based on triplicates.
[
[
13] S. Menichetti, R. Amorati, V. Meoni, L. Tofani, G. Caminati, C. Viglianisi,
Org. Lett. 2016, 18, 5464-5467.
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Napolitano, S. Menichetti, M. d’Ischia, Org. Biomol. Chem. 2015, 13,
5757-5764.
Thiol
Peroxidase
Acivity:
The
GPx-like
activities
of
dihydrobenzoselenophenes 8-11 were assessed by UV-spectroscopy at 305 nm
as the rate of formation of diphenyl disulfide (PhSSPh) following the protocol by
[
32]
[15] S. Kumar, J. Yan, J. Poon, V. P. Singh, X. Lu, M. K. Ott, L. Engman, S.
Tomoda
and catalyst (0.01 mM) at 21 C and the reaction was initiated by addition of
(3.75 mM) in methanol. The initial reduction rates calculated from the first
with slight modifications. The test mixture contained PhSH (1 mM)
o
Kumar, Angew. Chem. Int. Ed. 2016, 55, 3729-3733.
2 2
H O
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16] J. Malmström, M. Jonsson, I. A. Cotgreave, L. Hammarström, M. Sjödin,
L. Engman, J. Am. Chem. Soc. 2001, 123, 3434-3440.
7
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