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by-products. The aqueous solution was then acidified with HCl to
pH ꢀ1 over ice followed by extraction with ethyl acetate. The com-
bined ethyl acetate extracts were dried over MgSO4, filtered, con-
centrated, and purified by flash column chromatography (silica
gel, EtOAc/hexane, gradient). The purified product was dissolved
in acetonitrile and water (1:1, v/v) and dried by lyophilization.
Due to the instabilities of compounds 16 and 17 in ethyl acetate,
the reaction solutions of compounds 16 and 17 were lyophilized
followed by extraction with methanol. The crude products of 16
and 17 were purified by flash column chromatography (silica gel,
methanol/methylene dichloride).
J = 7.6, 14.0 Hz, 1H, CH2), 3.64 (dd, J = 4.8, 14.0 Hz, 1H, CH2), 4.74
(m, 1H, NCH), 7.66–7.38 (m, 2H, phenyl), 8.39–8.15 (m, 3H, phenyl,
2NH), 9.33 (s, 1H, OH). 13C NMR (acetone-d6): d 170.7, 169.5, 166.2,
143.3, 140.4, 124.7, 123.5, 122.9, 122.4, 51.8, 21.2, 21.5. MS: 362
(MH+). IR (cmÀ1): 3342, 1587, 1537, 1507.
5.1.2.7. N-Acetyl-S-(o-fluorophenylcarbamoyl)cysteine (6). The
title compound was obtained from the reaction of NAC with o-flu-
orophenylisocyanate. Yield, 61%; white solid, mp 65–70 °C. 1H
NMR (acetone-d6): d 1.97 (s, 3H, CH3), 3.34–3.23 (m, 1H, CH2),
3.62–3.51 (m, 1H, CH2), 4.73 (m, 1H, NCH), 7.21–7.12 (m, 3H, phe-
nyl), 7.59–7.46 (m, 1H, phenyl), 7.98–7.86 (m, 1H, NH), 9.25 (s, 1H,
NH). 13C NMR (acetone-d6): d 170.7, 169.6, 165.2, 154.6, 125.9,
125.8, 125.2, 124.1, 115.0, 52.2, 31.8, 21.5. MS: 301 (MH+). IR
(cmÀ1): 3269, 1650, 1614, 1524.
5.1.2.1. N-Acetyl-S-(p-chlorophenylcarbamoyl)cysteine (NACC). The
title compound was obtained from the reaction of NAC and p-chlo-
rophenylisocyanate in 80% yield. The spectral data were identical
to that reported earlier.9
5.1.2.8. N-Acetyl-S-(p-bromophenylcarbamoyl)cysteine (7). The
title compound was obtained from the reaction of NAC with
p-bromophenylisocyanate. Yield, 93%; white solid, mp 80–84 °C.
1H NMR (acetone-d6): d 1.97 (s, 3H, CH3), 3.33–3.23 (m, 1H, CH2),
3.62–3.53 (m, 1H, CH2), 4.73 (m, 1H, NCH), 7.67–7.39 (m, 5H, phe-
nyl, NH), 9.25 (s, 1H, NH). 13C NMR (acetone-d6): d 170.7, 169.7,
164.4, 138.0, 131.5, 120.6, 115.2, 52.2, 30.7, 21.5. MS: 363 (MH+).
IR (cmÀ1): 3281, 1659, 1589, 1524, 1483.
5.1.2.2. N-Acetyl-S-(p-fluorophenylcarbamoyl)cysteine (1). The
title compound was obtained from the reaction of NAC with p-flu-
orophenylisocyanate by following the procedure as described in
the method. Yield, 50%; white solid, mp 71–74 °C. 1H NMR (ace-
tone-d6): d 1.98 (s, 3H, CH3), 3.29 (dd, J = 7.6, 14.0 Hz, 1H, CH2),
3.58 (dd, J = 4.8, 14.0 Hz, 1H, CH2), 4.73 (m, 1H, NCH), 6.95–7.14
(m, 2H, phenyl), 7.66–7.45 (m, J = 9.2 Hz, 3H, phenyl, HN), 9.50
(s). 13C NMR (acetone-d6): d 170.7, 169.8, 164.3, 135.0, 120.7,
115.1, 114.9, 52.3, 30.7, 21.5. MS: 301 (MH+). IR (cmÀ1): 3277,
1724, 1655, 1618, 1536, 1507.
5.1.2.9. N-Acetyl-S-(2,5-dimethoxyphenylcarbamoyl)cysteine
(8). The title compound was obtained from the reaction of NAC
with 2,5-dimethoxyphenylisocyanate. Yield, 83%; white solid, mp
144–146 °C. 1H NMR (DMSO-d6): d 1.86 (s, 3H, CH3), 3.02 (dd,
J = 8.8, 13.8 Hz, 1H, CH2), 3.37 (dd, J = 4.8, 13.8 Hz, 1H, CH2), 4.36
(m, 1H, NCH), 6.68 (dd, J = 3.2, 9.0 Hz, 1H, phenyl), 6.96
(d, J = 8.8 Hz, 1H, phenyl), 7.31 (s, 1H, phenyl), 8.29 (d, J = 8.0 Hz,
1H, NH), 9.53 (s, 1H, NH). 13C NMR (DMSO-d6): d 170.8, 168.2,
163.7, 151.6, 143.5, 126.2, 123.2, 11.2, 108.3, 55.0, 54.2, 51.1,
29.5 21.2. MS: 343 (MH+). IR (cmÀ1): 3322, 1687, 1605, 1516.
5.1.2.3. N-Acetyl-S-(naphthalen-1-ylcarbamoyl)cysteine (2). The
title compound was obtained from the reaction of NAC with 1-isocy-
anatonaphthalene following the procedure as described in the meth-
od. Yield, 87%; white solid, mp 128–131 °C. 1H NMR (DMSO-d6): d
1.87 (s, 3H, CH3), 3.08 (dd, J = 8.4, 13.6 Hz, 1H, CH2), 3.42 (dd, J = 4.8,
13.6 Hz, 1H, CH2), 4.42 (m, 1H, NCH), 7.60–7.46 (m, 4H, phenyl),
7.82 (d, J = 8.0 Hz, 1H, phenyl), 8.02–7.92 (m, 2H, phenyl), 8.29
(d, J = 8.0 Hz, 1H, NH), 10.36 (s, 1 H). 13C NMR (DMSO-d6): d 170.8,
168.1, 164.8, 132.6, 132.1, 127.3, 126.9, 125.1, 125.0, 124.4, 121.9,
121.7, 116.9, 51.1, 29.7, 21.3. MS: 333 (MH+). IR (cmÀ1): 3265, 1724,
1650, 1524, 1495.
5.1.2.10. N-Acetyl-S-(p-iodophenylcarbamoyl)cysteine (9). The
title compound was obtained from the reaction of NAC with p-iod-
ophenylisocyanate. Yield, 75%; white solid, mp 92–95 °C. 1H NMR
(acetone-d6): d 1.97 (s, 3H, CH3), 3.29 (dd, J = 7.6, 14.0 Hz, 1H,
CH2), 3.58 (dd, J = 4.4, 14.0 Hz, 1H, CH2), 4.73 (m, 1H, NCH), 7.33
(d, J = 8.4 Hz, 2H, phenyl), 7.55 (d, J = 7.6 Hz, 1H, NH), 7.66
(d, J = 8.4 Hz, 2H, phenyl), 9.55 (s, 1H, NH). 13C NMR (acetone-
d6): d 170.7, 169.6, 164.4, 138.6, 137.5, 120.9, 85.8, 52.2, 30.8,
21.5. MS: 409 (MH+). IR (cmÀ1): 3284, 1659, 1581, 1520.
5.1.2.4. N-Acetyl-S-(o-methylsulfanylphenylcarbamoyl)cysteine
(3). The title compound was obtained from the reaction of NAC
with o-methylsulfanylphenylisocyanate. Yield, 69%; white solid,
mp 55–60 °C. 1H NMR (acetone-d6): d 1.96 (s, 3H, CH3), d 2.43
(s, 3H, CH3), 3.33–3.23 (m, 1H, CH2), 3.59–3.49 (m, 1H, CH2), 4.71
(m, 1H, NCH), 7.33–7.15 (m, 2H, phenyl), 7.55–7.38 (m, 2H, phe-
nyl), 7.69 (d, J = 6.8 Hz, 1H, NH), 8.75 (s, 1H, NH). 13C NMR (ace-
tone-d6): d 172.3, 171.2, 167.0, 137.5, 130.6, 128.0, 127.5, 125.9,
125.8, 53.9, 32.4, 23.1, 17.4. MS: 329 (MH+). IR (cmÀ1): 3291,
1732, 1642, 1499.
5.1.2.11. N-Acetyl-S-(o-nitro-p-trifluoromethylphenylcarbamoyl)
cysteine (10). The title compound was obtained from the reactionof
NAC with o-nitro-p-trifluoromethylphenylisocyanate. Yield, 52%;
light yellow solid, mp 69–72 °C. 1H NMR (DMSO-d6): d 1.87 (s, 3H,
CH3), 3.11 (dd, J = 8.8, 13.4 Hz, 1H, CH2), 3.41 (dd, J = 5.2, 13.6 Hz,
1H, CH2), 4.37 (m, 1H, NCH), 7.82 (d, J = 8.4 Hz, 1H, phenyl), 8.09
(dd, J = 2.0, 8.8 Hz, 1H, phenyl), 8.34–8.27 (m, 2H, phenyl, NH),
11.05 (br, 1H). 13C NMR (DMSO-d6): d 170.9, 168.2, 165.0, 140.4,
133.0, 129.5, 124.6, 121.6, 120.5, 50.8, 29.8, 21.2, 19.9. MS: 396
(MH+). IR (cmÀ1): 3309, 1626, 1581, 1512.
5.1.2.5. N-Acetyl-S-(o-methoxyphenylcarbamoyl)cysteine (4). The
title compound was obtained from the reaction of NAC with
o-methoxyphenylisocyanate. Yield, 87%; white solid, mp 62–65 °C.
1H NMR (acetone-d6): d 1.96 (s, 3H, CH3), 3.25–3.33 (m, 1H, CH2),
3.60–3.53 (m, 1H, CH2), d 3.86 (s, 3H, OCH3), 4.71 (m, 1H, NCH),
7.11–6.89 (m, 3H, phenyl), 7.54 (d, J = 5.2 Hz, 1H, phenyl), 8.01
(d, J = 8.0 Hz, 1H, NH), 8.60 (s, 1H, NH). 13C NMR (acetone-d6): d
170.7, 169.5, 164.3, 148.8, 127.2, 124.2, 120.6, 120.2, 110.5, 55.0,
52.2, 30.8, 21.5. MS: 313 (MH+). IR (cmÀ1): 3319, 1733, 1652, 1602,
1518.
5.1.2.12. N-Acetyl-S-(o-methoxybenzylcarbamoyl)cysteine
(11). The title compound was obtained from the reaction of NAC
with o-methoxybenzylisocyanate. Yield, 61%; white solid, mp
63–65 °C. 1H NMR (acetone-d6): d 1.90 (s, 3H, CH3), 3.23 (dd,
J = 8.4, 14.0 Hz, 1H, CH2), 3.46 (dd, J = 4.4, 14.0 Hz, 1H, CH2), 3.84
(s, 3H, OCH3), 4.43(m, 2H, CH2), 4.61 (m, 1H, NCH), 6.99–6.86 (m,
2H, phenyl), 7.29–7.21 (m 2H, phenyl), 7.46 (d, J = 7.2 Hz, 1H,
NH), 7.67 (s, 1H, NH). 13C NMR (acetone-d6): d 170.7, 169.6,
165.8, 156.9, 128.2, 126.0, 120.0, 110.0, 54.5, 52.8, 39.7, 30.4,
21.5. MS: 327 (MH+). IR (cmÀ1): 3311, 1654, 1493.
5.1.2.6. N-Acetyl-S-(o-chloro-p-nitrophenylcarbamoyl)cysteine
(5). The title compound was obtained from the reaction of NAC
with o-chloro-p-nitrophenylisocyanate. Yield, 31%; white solid,
mp 56–59 °C. 1H NMR (acetone-d6): d 1.98 (s, 3H, CH3), 3.33 (dd,