PAPER
N-Acylated Photoactivatable Analogues of Glutathione
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1 H, Glua), 4.70 (m, 2 H, Glya), 2.59 (m, 2 H, Cysb), 2.48 (m, 3 H,
Glug + Glub1), 2.09 (m, 1 H, Glub2).
13C NMR (62.5 MHz, D2O): d = 200.06, 175.80, 175.66, 171.55,
169.37, 139.69, 137.46, 136.36, 133.83, 130.42, 130.39, 128.62,
127.33, 55.45, 55.42, 43.24, 32.25, 27.23, 25.67.
MS (MALDI-TOF): m/z = 758 [M + H]+, 780 [M + Na]+, 796 [M +
K]+.
N-(4-Azidobenzoyl)glutathione (1a)
White solid; yield: 70%.
MS (ESI–): m/z = 756.2 [M – H]–.
1H NMR (250 MHz, D2O): d = 7.88–7.82 (m, 2 H), 7.26–7.20 (m, 2
H), 4.59–4.53 (m, 2 H, Cysa + Glua), 3.91 (s, 2 H, Glya), 2.97 (br
s, 2 H, Cysb), 2.60 (m, 2 H, Glug), 2.39 (m, 1 H, Glub1), 2.22 (m, 1
H, Glub2).
13C NMR (62.5 MHz, D2O): d = 175.20, 172.79, 172.26, 163.25,
146,03, 132,06, 131,38, 121,41, 55.45, 55.42, 43.24, 32.25, 27.23,
25.67.
Anal. Calcd for C43H39N3O8S: C, 68.15; H, 5.19; N, 5.54. Found: C,
68.23; H, 5.28; N, 5.47.
N-(4-Azidobenzoyl)-S-tritylglutathione (8a)
White solid; yield: 55%; mp 210 °C.
1H NMR (250 MHz, D2O): d = 7.84–7.78 (m, 2 H), 7.70–7.30 (m,
15 H), 7.23–7.17 (m, 2 H), 4.57 (m, 1 H, Cysa), 4.00 (m, 1 H, Glua),
3.70 (m, 2 H, Glya), 2.70 (m, 2 H, Cysb), 2.48 (m, 2 H, Glug), 2.40
(m, 1 H, Glub1), 2.09 (m, 1 H, Glub2).
MS (ESI–): m/z = 451.1 [M – H]–.
Anal. Calcd for C17H20N6O7S: C, 45.13; H, 4.46; N, 18.57. Found:
C, 45.21; H, 4.53; N, 18.72.
MS (ESI–): m/z = 693.2 [M – H]–.
Anal. Calcd for C36H34N6O7S: C, 62.24; H, 4.93; N, 12.10. Found:
C, 62.11; H, 5.05; N, 12.00.
N-(3-Azido-4-chlorobenzoyl)glutathione (1c)
White solid; yield: 75%.
N-(3-Azido-4-chlorobenzoyl)-S-tritylglutathione (8c)
White solid; yield: 63%; mp 200 °C.
1H NMR (250 MHz, D2O): d = 7.70 (m, 1 H), 7.59 (m, 2 H), 7.43
(m, 15 H), 4.57 (m, 1 H, Cysa), 4.00 (m, 1 H, Glua), 3.69 (m, 2 H,
Glya), 2.69 (m, 2 H, Cysb), 2.48 (m, 2 H, Glug), 2.22 (m, 1 H,
Glub1), 2.10 (m, 1 H, Glub2).
1H NMR (250 MHz, D2O): d = 7.78 (s, 1 H), 7.63–7.59 (m, 2 H),
4.60 (t, J = 6.25 Hz, 1 H, Cysa), 4.45 (m, 1 H, Glua), 3.70 (s, 2 H,
Gly), 2.95 (d, J = 5.5 Hz, 2 H, Cysb), 2.59 (m, 2 H, Glug), 2.35 (m,
1 H, Glub1), 2.20 (m, 1 H, Glub2).
13C NMR (62.5 MHz, D2O): d = 176.09, 175.83, 171.46, 168.15,
137.52, 133.44, 130.75, 127.71, 124.37, 118.82, 55.54, 55.40,
43.21, 32.33, 27.13, 25.77.
MS (ESI–): m/z = 727.1 [M – H]–.
MS (ESI–): m/z = 485.1 [M – H]–.
Anal. Calcd for C36H33ClN6O7S: C, 59.30; H, 4.56; N, 11.52.
Found: C, 59.17; H, 4.67; N, 11.62.
Anal. Calcd for C17H19ClN6O7S: C, 41.94; H, 3.93; N, 17.26.
Found: C, 50.11; H, 4.07; N, 17.29.
N-(2-Azido-4-nitrobenzoyl)-S-tritylglutathione (8d)
Pale yellow solid; yield: 48%; mp 221 °C (dec).
N-(2-Azido-4-nitrobenzoyl)glutathione (1d)
Yellow solid; yield: 74%.
1H NMR (250 MHz, D2O): d = 8.31 (s, 1 H), 8.17 (m, 1 H), 7.96–
7.92 (m, 1 H), 4.62 (m, 1 H, Cysa), 4.49 (m, 1 H, Glua), 3.79 (s, 2
H, Glya), 2.97 (d, J = 4 Hz, 2 H, Cysb), 2.61 (m, 2 H, Glug), 2.40
(m, 1 H, Glub1), 2.20 (m, 1 H, Glub2).
1H NMR (250 MHz, D2O): d = 8.10 (s, 1 H), 8.05 (m, 1 H), 7.83 (m,
1 H), 7.43 (m, 15 H), 4.45 (m, 1 H, Cysa), 3.85 (m, 1 H, Glua), 3.75
(m, 2 H, Glya), 2.70 (m, 2 H, Cysb), 2.48 (m, 2 H, Glug), 2.37 (m,
1 H, Glub1), 2.09 (m, 1 H, Glub2).
MS (ESI–): m/z = 738.1 [M – H]–.
13C NMR (62.5 MHz, D2O): d = 175.69, 171.91, 162.70, 149.52,
139.37, 130.99, 119.68, 114.78, 111.77, 55.47, 52.43, 43.35, 32.04,
27.46, 25.67.
Anal. Calcd for C36H33N7O9S: C, 58.45; H, 4.50; N, 13.25. Found:
C, 58.59; H, 4.57; N, 13.13.
N-(5-Azido-2-nitrobenzoyl)-S-tritylglutathione (8e)
Pale yellow solid; yield: 66%; mp 225 °C (dec).
MS (ESI–): m/z = 496.2 [M – H]–.
Anal. Calcd for C17H19N7O9S: C, 41.05; H, 3.85; N, 19.71. Found:
C, 41.01; H, 3.98; N, 19.61.
1H NMR (250 MHz, D2O): d = 8.25 (m, 1 H), 7.60–7.25 (m, 17 H),
4.45 (m, 1 H, Cysa), 3.85 (m, 1 H, Glua), 3.75 (m, 2 H, Glya), 2.78
(m, 2 H, Cysb), 2.48 (m, 2 H, Glug), 2.37 (m, 1 H, Glub1), 2.09 (m,
1 H, Glub2).
N-(5-Azido-2-nitrobenzoyl)glutathione (1e)
Yellow solid; yield: 79%.
MS (ESI–): m/z = 737.9 [M – H]–.
1H NMR (250 MHz, D2O): d = 8.33–8.29 (m, 1 H), 7.43–7.41 (m, 2
H), 4.67 (m, 1 H, Cysa), 4.52 (m, 1 H, Glua), 3.85 (s, 2 H, Glya),
3.00 (m, 2 H, Cysb), 2.57 (m, 2 H, Glug), 2.37 (m, 1 H, Glub1), 2.10
(m, 1 H, Glub2).
13C NMR (62.5 MHz, D2O): d = 175.69, 171.88, 168.10, 147.44,
141.00, 133.68, 127.36, 120.59, 119.16, 55.14, 52.59, 43.35, 32.48,
27.54, 25.28.
Anal. Calcd for C36H33N7O9S: C, 58.45; H, 4.50; N, 13.25. Found:
C, 58.39; H, 4.55; N, 13.37.
N-Substituted GSH Analogues 1 and 3; General Procedure
Et3SiH (8 mL, 0.052 mmol, 2 equiv) were added to a soln of 5 or
8a,c–e (0.026 mmol) in a mixture of CH2Cl2 (1 mL) and of TFA (0.5
mL). The mixture was then stirred at r.t for 90 min and concentrated
under reduced pressure. The crude residue was column chromato-
graphed (silica gel, MeCN–H2O, 9:1).
MS (ESI–): m/z = 496.0 [M – H]–.
Anal. Calcd for C17H19N7O9S: C, 41.05; H, 3.85; N, 19.71. Found:
C, 41.08; H, 3.94; N, 19.86.
N-(4-Benzoylbenzoyl)glutathione (3)
Beige solid; yield: 71%.
1H NMR (250 MHz, D2O): d = 7.97–7.86 (m, 6 H), 7.80 (m, 1 H),
7.66 (t, J = 9.2 Hz, 2 H), 4.60 (t, J = 6.9 Hz, 1 H, Cysa), 4.57 (m, 1
H, Glua), 3.75 (s, 2 H, Glya), 2.95 (d, J = 8.3 Hz, 2 H, Cysb), 2.60–
2.58 (m, 2 H, Glug), 2.40 (m, 1 H, Glub1), 2.20 (m, 1 H, Glub2).
Acknowledgment
The authors would like to thank Dr G. L. Sommen for his help in
bibliographic research, Mrs V. Poddig for NMR spectra recording
and LSMCL-Metz for MALDI-TOF recording.
Synthesis 2007, No. 1, 140–144 © Thieme Stuttgart · New York