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V. Silvia et al. / European Journal of Medicinal Chemistry 50 (2012) 383e392
(m, 1H, CH); 6.63e6.83 (m, 3H, Ar); 7.23e7.37 (m, 15H, trityl-H);
8.51 (d, J ¼ 8, 1H, NH); 8.78 (br s, 1H, OH).
MALDI-TOF MS: m/z 542.6 Da [M þ H]þ, C32H31NO5S, Mol. Wt.:
541.66.
MALDI-TOF MS: m/z 312.5 Da [M þ H]þ, C14H17NO5S, Mol. Wt.:
311.35.
3.1.18. 2-[3-(4-Hydroxy-3,5-dimethoxy-phenyl)-acryloylamino]-3-
mercapto-propionic acid methyl ester (11)
3.1.12. 2-[3-(4-Hydroxy-phenyl)-acryloylamino]-3-trytilsulphanil-
propionic acid methyl ester (18)
Grad.: CH2Cl2/MeOH, 100:0/98:2, 63% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.59 (t, J ¼ 8.4 Hz, 1H, SH); 2.80e2.93
Grad.: CH2Cl2/MeOH, 100:0/98:2, 30% yield, pale-yellow foam.
(m, 2H, CH2); 3.67 (s, 3H, CO2CH3); 3.80 (s, 6H, 2 ꢂ OCH3);
4.59e4.62 (m, 1H, CH); 6.62 (d, J ¼ 15.6 Hz, 1H, CH ¼ CHb); 6.88 (s,
2H, Ar); 7.36 (d, J ¼ 15.6 Hz, 1H, CHa ¼ CH); 8.38 (d, J ¼ 8 Hz, 1H,
NH); 8.85 (br s, 1H, OH).
1H NMR (DMSO):
d (ppm) 2.46e2.56 (m, 2H, CH2); 3.57 (s, 3H,
CO2CH3); 4.22e4.35 (m, 1H, CH); 6.47 (d, J ¼ 16.2 Hz, 1H, CH ¼ CHb);
6.79 (d, J ¼ 8.4 Hz, 2H, Ar); 7.25e7.38 (m, 16H, trityl-H, Ar,
CHa ¼ CH); 8.40 (d, J ¼ 8 Hz, 1H, NH); 9.88 (br s, 1H, OH).
MALDI-TOF MS: m/z 524.7 Da [M þ H]þ, C32H29NO4S, Mol. Wt.:
523.64.
MALDI-TOF MS: m/z342.5 Da [M þ H]þ, C15H19NO6S, Mol. Wt.:
341.38.
3.1.19. 2-[3-(4-Hydroxy-3-methoxy-phenyl)-acryloylamino]-3-
mercapto-propionic methyl ester (13)
3.1.13. 2-[3-(3-Hydroxy-phenyl)-acryloylamino]-3-
trytilsulphanùyl-propionic acid methyl ester (20)
Grad.: CH2Cl2/MeOH, 100:0/98:2, 46% yield, pale-yellow foam.
Grad.: CH2Cl2/MeOH, 100:0/98:2, 72% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.63 (t, J ¼ 8 Hz, 1H, SH); 2.86e3.02
1H NMR (DMSO):
d
(ppm) 2.52e2.62 (m, 2H, CH2); 3.58 (s, 3H,
(m, 2H, CH2); 3.66 (s, 3H, CO2CH3); 3.81 (s, 6H, 2 ꢂ OCH3);
4.53e4.57 (m, 1H, CH); 7.22 (s, 2H, Ar); 8.63 (d, J ¼ 7.6, 1H, NH); 9.04
(br s, 1H, OH).
CO2CH3); 4.27e4.31 (m, 1H, CH); 6.62 (d, J ¼ 16 Hz, 1H, CH ¼ CHb);
6.78e7.01 (m, 3H, Ar); 7.21e7.38 (m, 16H, trityl-H, CHa ¼ CH, Ar);
8.60 (d, J ¼ 8.2, 1H, NH); 9.60 (br s, 1H, OH).
MALDI-TOF MS: m/z312.5 Da [M þ H]þ, C14H17NO5S, Mol. Wt.:
311.35.
MALDI-TOF MS: m/z 524.8 Da [M þ H]þ, C32H29NO4S, Mol. Wt.:
523.64.
3.1.20. 2-[2-(3,4-Dihydroxy-phenyl)-acetylamino]-3-mercapto-
propionic acid methyl ester (15)
3.1.14. 2-[3-(2-Hydroxy-phenyl)-acryloylamino]-3-trytilsulphanyl-
propionic acid methyl ester (22)
Grad.: CH2Cl2/MeOH, 100:0/99:1, 55% yield, pale-yellow foam.
Grad.: CH2Cl2/MeOH, 100:0/98:2, 34% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.47 (t, J ¼ 8.4 Hz, 1H, SH); 2.73e2.81
1H NMR (DMSO):
d
(ppm) 2.42e2.63 (m, 2H, CH2); 3.57 (s, 3H,
(m, 2H, CH2); 3.29 (s, 2H, CH2); 3.64 (s, 3H, CO2CH3); 4.40e4.45 (m,
1H, CH); 6.45e6.66 (m, 3H, Ar); 8.41 (d, J ¼ 8, 1H, NH); 9.69, 8.78 (br
s, 2H, 2 ꢂ OH).
CO2CH3); 4.25e4.31 (m, 1H, CH); 6.73 (d, J ¼ 16 Hz, 1H, CH ¼ CHb);
6.81e6.90 (m, 2H, Ar); 7.16e7.21 (m, 1H, Ar); 7.26e7.39 (m, 15H,
trityl-H); 7.41e7.45 (m, 1H, Ar); 7.62 (d, J ¼ 16 Hz, 1H, CHa ¼ CH);
7.56 (d, J ¼ 8, 1H, NH); 10.08 (br s, 1H, OH).
MALDI-TOF MS: m/z286.4 Da [M þ H]þ, C12H15NO5S, Mol. Wt.:
285.32.
MALDI-TOF MS: m/z 524.5 Da [M þ H]þ, C32H29NO4S, Mol. Wt.:
523.64.
3.1.21. 2-[2-(4-hydroxy-3-methoxy-phenyl)-acetylamino]-3-
mercapto-propionic acid methyl ester (17)
3.1.15. General procedure: deprotection of thiolic group of the
cysteine-phenolic acids conjugates
Grad.: CH2Cl2/MeOH, 100:0/98:2, 79% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.51 (t, J ¼ 8.4 Hz, 1H, SH); 2.74e2.85
The opportune trytilated derivative (6, 8, 10, 12, 14, 16, 18, 20, 22)
(1 mmol) was treated with a solution of TFA, Et3Si and CH2Cl2 (4/4/
92 v/v). The reaction mixture was stirred 5e6 h and then a sat.d aq.
NaHCO3 solution was added; the solution was extracted with
CH2Cl2. The organic phase was dried, filtered and evaporated to give
a crude residue purified by chromatography over silica gel to afford
the desired products.
(m, 2H, CH2); 3.38 (s, 2H, Ar-CH2); 3.63 (s, 3H, OCH3); 3.74 (s, 3H,
CO2CH3); 4.42e4.47 (m, 1H, CH); 6.65e6.85 (m, 3H, Ar); 8.44 (d,
J ¼ 7.6 Hz, 1H, NH); 8.78 (br s, 1H, OH).
MALDI-TOF MS: m/z 300.5 Da [M þ H]þ, C13H17NO5S, Mol. Wt.:
299.34.
3.1.22. 2-[3-(4-hydroxy-phenyl)-acryloylamino]-3-mercapto-
propionic acid metyl ester (19)
3.1.16. 2-[3-(3,4-Dihydroxy-phenyl)-acryloylamino]-3-mercapto-
propionic acid methyl ester (7)
Grad.: CH2Cl2/MeOH, 100:0/98:2, 38% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.56 (t, J ¼ 8.4 Hz, 1H, SH); 2.81e2.87
Grad.: CH2Cl2/MeOH, 100:0/95:5, 31% yield, pale-yellow foam.
(m, 2H, CH2); 3.66 (s, 3H, CO2CH3); 4.57e4.60 (m, 1H, CH); 6.53 (d,
J ¼ 15.6 Hz, 1H, CH ¼ CHb); 6.78e6.70 (m, 2H, Ar); 7.36 (d,
J ¼ 15.6 Hz,1H, CHa ¼ CH); 7.40e7.43 (m, 2H, Ar); 8.43 (d, J ¼ 7.6,1H,
NH); 9.88 (br s, 1H, OH).
1H NMR (DMSO):
d
(ppm) 2.59 (t, J ¼ 8.8 Hz, 1H, SH); 2.84e2.86
(m, 2H, CH2); 3.66 (s, 3H, CO2CH3); 4.45e4.60 (m, 1H, CH); 6.45 (d,
J ¼ 15.6 Hz, 1H, CH ¼ CHb); 6.73e6.97 (m, 3H, Ar); 7.28 (d,
J ¼ 15.6 Hz, 1H, CHa ¼ CH); 8.43 (d, J ¼ 8.2, 1H, NH); 9.18, 9.38 (br s,
2H, OH).
MALDI-TOF MS: m/z282.6 Da [M þ H]þ, C13H15NO4S, Mol. Wt.:
281.33.
MALDI-TOF MS: m/z298.5 Da [M þ H]þ, C13H15NO5S, Mol. Wt.:
297.33.
3.1.23. 2-[3-(3-hydroxy-phenyl)-acryloylamino]-3-mercapto-
propionic acid methyl ester (21)
3.1.17. 2-[3-(4-Hydroxy-3-methoxy-phenyl)-acryloylamino]-3-
mercapto-propionic methyl ester (9)
Grad.: CH2Cl2/MeOH, 100/0/98/2, 42% yield, pale-yellow foam.
1H NMR (DMSO):
d
(ppm) 2.60 (t, J ¼ 8.4 Hz, 1H, SH); 2.80e2.91
Grad.: CH2Cl2/MeOH, 100:0/98:2, 46% yield, yellow-pale foam.
(m, 2H, CH2); 3.67 (s, 3H, CO2CH3); 4.57e4.61 (m, 1H, CH); 6.67 (d,
J ¼ 16 Hz, 1H, CH ¼ CHb); 6.78e6.81 (m, 1H, Ar); 6.94e7.01 (m, 2H,
Ar); 7.19e7.24 (m, 1H, Ar); 7.36 (d, J ¼ 16 Hz, 1H, CHa ¼ CH); 8.57 (d,
J ¼ 8 Hz, 1H, NH); 9.61 (br s, 1H, OH).
1H NMR (DMSO):
d
(ppm) 2.59 (t, J ¼ 8.2 Hz, 1H, SH); 2.80e2.95
(m, 2H, CH2); 3.66 (s, 3H, OCH3); 3.80 (s, 3H, CO2CH3); 4.55e4.62
(m, 1H, CH); 6.58 (d, J ¼ 16 Hz, 1H, CH ¼ CHb); 6.78e7.15 (m, 3H,
Ar); 7.35 (d, J ¼ 16 Hz, 1H, CHa ¼ CH); 8.40 (d, J ¼ 8 Hz,1H, NH); 9.49
(br s, 1H, OH).
MALDI-TOF MS: m/z282.5 Da [M þ H]þ, C13H15NO4S, Mol. Wt.:
281.33.