6962 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 19
Doering et al.
redox catalysts. There is clearly considerable scope to explore
further the effects of redox catalysts on various cells, tissues,
and organs.
0.85 mmol), NaBH4 (129.5 mg, 3.42 mmol), and 2,3-dichloro-
1,4-naphthoquinone (97 mg, 0.43 mmol) following the general
procedure described in the Supporting Information. Its formation
was monitored by TLC (petroleum ether/ethyl acetate, 9:1 v/v):
Rf = 0.20. Compound 9 was purified by column chromatography
on silica gel using petroleum ether/ethyl acetate (9.7:0.3 v/v) as
solvent. Yield 44%, deep orange crystals, mp 68 ꢀC. 1HNMR:8.06
- 8.02 (dd, J(H,H) = 3.19, 2.56 Hz, 2H, H-5, H-6 or H-7, H-8),
7.67-7.65 (dd, J(H,H) = 3.19, 2.56 Hz, 2H, H-5, H-6 or H-7,
H-8), 4.84-4.82 (t, J(H,H) = 5.66 Hz, 2H, H-10), 3.71-3.52 (m,
8H, C2H5), 3.42-3.41 (d, J(H,H) = 5.74 Hz, 4H, H-9), 1.17-1.15
(t, J(H,H) = 6.9 Hz, 12H, C2H5) ppm. 13C NMR: 178.6 (2C),
149.9 (2C), 133.2 (2C), 132.9 (2C), 127.1 (2C), 102.6 (2C), 62.2
(4C), 32.4 (2C), 15.1 (4C) ppm. HPLC: tR = 7.420 min, purity
99.2%. HRMS (m/z): [M]þ calcd for C22H30O6Se2, 550.0372;
found 550.0223.
5. Materials and Methods
5.1. Materials. Chemical reagents were purchased from Sig-
ma-Aldrich-Fluka (Steinheim, Germany) and used without
further purification unless stated otherwise. For chemical synth-
esis, reactions were carried out in distilled water or in laboratory
grade solvents at room temperature and under nitrogen atmo-
sphere. Purification was carried out by column chromatography
using silica gel (Macherey-Nagel, 50-200 μm diameter) under
nitrogen pressure. Melting points were recorded using a digital
melting point apparatus (IA9000 series, ThermoFischer Scientific,
Rochford, U.K.) and are given without correction. 1H NMR
spectra were recorded at 500 MHz, and 13C NMR spectra were
recorded at 125 MHz on a Bruker Avance 500 spectrometer.
Chemical shifts are reported in δ (ppm), expressed relative to the
solvent signal at 7.26 ppm (CDCl3, 1H NMR) and at 77.16 ppm
(CDCl3, 13C NMR). Compounds were determined to exceed 95%
purity by HPLC recorded on a Bischoff Lambda 1000 UV/vis at
275nmusingaYMCC18Procolumnandmethanol/water(85:15)
as mobile phase at a flow rate of 1.0 mL/min. IR data were
measured on a Bruker Tensor 27 using a golden gate. HRMS were
recorded on a Finnigan MAT 95 spectrometer using the Ci
positive technique. UV/vis spectra were recorded on a CARY
50Bio spectrophotometer (Varian Inc.), with quartz cells used
throughout. All recordings were taken at 18 ꢀC and repeated at
least three times.
Acknowledgment. This work was supported financially by
Saarland University, Germany, the Ministry of Economics
and Science of Saarland, DFG Grants JA1741/2-1 and
HE3553/2-1, the European Community’s Seventh Framework
Programme (FP7/2007-2013) under Grant Agreement 215009
RedCat, and a Deutsche Krebshilfe Max-Eder Young Inves-
tigator’s Award (M.H.). N.L. received a stipend from the
Cologne University and Bayer Health Care Preferred Partner-
ship Pharmacology Program. IR measurements were per-
formed by A. Engelke in the Wenz laboratory (Saarland
University). C.S. was financed by a grant from the Fonds
National pour la Recherche (FNR), Luxembourg. M.D.’s
research is supported by the “Recherche Cancer et Sang”
foundation, by the “Recherches Scientifiques Luxembourg”
Please note that some of the compounds can be sensitive to
oxidation and light. They should therefore be stored under
protective gas at low temperature and in the dark.
5.2. Methods. Reactions were carried out under a protective
N2 atmosphere. Full details for all compounds are provided in
the Supporting Information.
€
asbl, by the “Een Haerz fir Kriibskrank Kanner” association,
the Action Lions “Vaincre le Cancer” Luxembourg and Tele-
vie Luxembourg.
2,3-Bis(phenylselanyl)-5,8-dihydroxynaphthoquinone 7 was syn-
thesized from diphenyldiselenide (57.3 mg, 0.15 mmol), NaBH4
(32.6 mg, 8.58 mmol), and 2,3-dichloro-5,8-dihydroxy-1,4-naptho-
quinone (74.8 mg, 0.29 mmol) following the general procedure
described in the Supporting Information. Its formation was mon-
itored by TLC (petroleum ether/ethyl acetate, 9:1 v/v): Rf = 0.45.
Compound 7 was purified by column chromatography on silica gel
using petroleum ether/ethyl acetate (9:1 v/v) as solvent. Yield 27%,
deep orange-red crystals, mp 166-167 ꢀC. 1H NMR: 12.30 (s, 2H,
H-6, H-7), 7.55-7.53 (m, 4H, H-a), 7.36-7.31 (m, 6H, H-b, H-c)
ppm. 13C NMR: 181.3 (2C), 159.0 (2C), 152.0 (2C), 133.4 (4C),
130.7 (2C), 129.4 (4C), 129.3 (2C), 128.1 (2C), 111.7 (2C) ppm.
HPLC: tR = 16.748 min, purity 99.8%. HRMS (m/z): [M]þ calcd
for C22H14O4Se2, 501.9222; found 501.9472.
Supporting Information Available: General and specific pro-
cedures for the synthesis of the remaining compounds; addi-
tional analytical data for 7, 8, and 9; and detailed information
regarding the various biological and cell culture assays. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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2-(Hydroxyphenyltellanyl)-3-methylnaphthoquinone
8 was
synthesized from 4-hydroxyphenyltellurium trichloride (598.4 mg,
1.83 mmol), NaBH4 (310.1 mg, 8.16 mmol), and 3-bromo-2-
methyl-1,4-naphthoquinone (458.0 mg, 1.82 mmol) following
the general procedure described in the Supporting Information
(in this particular case, a tellurium trichloride instead of ditel-
luride was used, demanding more reducing agent). Its formation
was monitored by TLC (petroleum ether/ethyl acetate, 8:2 v/v):
Rf = 0.33. Compound 8 was purified by column chromatogra-
phy on silica gel using petroleum ether/ethyl acetate (8.5:1.5 v/v)
as solvent. Yield 18%, deep purple crystals, mp 161 ꢀC. 1H
NMR: 8.06-8.03 (m, 2H, H-5, H-8), 7.74-7.63 (m, 4H, H-a or
H-b, H-6, H-7), 6.74-6.71 (m, 2H, H-a or H-b), 5.03 (br s, OH),
1.92 (s, 3H, CH3) ppm. 13C NMR: 184.8 (C), 181.6 (C), 179.8
(C), 156.7 (C), 153.4 (C), 142.5 (2C), 134.1 (C), 133.5 (C), 132.2
(C), 131.8 (C), 127.2 (C), 127.1 (C), 117.1 (2C), 103.4 (C), 19.6
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