520
K. Lee et al. / European Journal of Medicinal Chemistry 62 (2013) 515e525
J ¼ 9.6 Hz, 1H), 7.29 (s, 1H), 3.99 (s, 6H), 3.23 (m, 1H), 2.90 (m, 1H),
J ¼ 10 Hz, 1H), 7.30 (s, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.19 (m, 1H),
13
1
.1 (m, 1H), 1.69 (m, 1H), 1.39 (m, 6H), 0.89 (t, J ¼ 7.2 Hz, 3H);
NMR (CDCl , 100 MHz) 182.0 (C-1), 181.8 (C-4), 154.6 (C-5), 154.4
C-8), 154.2 (C-2), 136.8 (C-3), 121.7 (C-7), 120.8 (C-6), 120.4 (C-9),
C
2.89 (m, 1H), 1.89 (m, 1H), 1.55 (m, 1H), 1.41 (2H), 1.22 (m, 14H), 0.83
1
3
3
d
(t, J ¼ 7.6 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d 182.0 (C-1), 181.9 (C-
(
1
4),154.6 (C-5),154.4 (C-8),154.3 (C-2), 136.9 (C-3),121.6 (C-7),120.9
0
0
20.1 (C-10), 56.9 (OCH
3
), 56.7 (OCH
3
), 53.7 (C-1 ), 30.6 (C-2 ), 22.2
(C-6), 120.3 (C-9), 120.1 (C-10), 56.8 (OCH
3
), 56.7 (OCH
3
), 53.7 (C-
0
0
0
þ
0
0
0
0
0
0
(
C-3 ), 21.8 (C-4 ), 13.7 (C-5 ); ESI-MS: m/z 358.9 (M þ Na) .
1 ), 31.9 (C-2 ), 29.5 (C-3 ), 29.5 (C-4 ), 29.3 (C-5 ), 29.3 (C-6 ), 29.2
0
0
0
0
0
(
C-7 ), 28.5 (C-8 ), 22.6 (C-9 ), 22.2 (C-10 ), 14.1 (C-11 ); ESI-MS: m/z
þ
5
.1.6. 2-Hexylsulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3f)
It was obtained from 2f as a red solid in 76.7% yield; mp 120 C;
H NMR (CDCl , 400 MHz)
7.42 (d, J ¼ 9.6 Hz, 1H), 7.37 (d,
443.0 (M þ Na) .
ꢀ
1
3
d
5.1.12. 2-Dodecylsulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3l)
ꢀ
1
J ¼ 9.6 Hz, 1H), 7.30 (s, 1H), 4.00 (s, 3H), 3.99 (s, 3H), 3.29 (m, 1H),
It was obtained from 2l as a red solid in 33% yield; mp 104 C; H
2
0
.91 (m, 1H), 1.91 (m, 1H), 1.67 (m, 1H), 1.45 (m, 2H), 1.29 (m, 4H),
NMR (CDCl
3
, 400 MHz)
d
7.41 (d, J ¼ 9.6 Hz, 1H), 7.30 (d, J ¼ 9.6 Hz,
13
.87 (t, J ¼ 7.2 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d 182.0 (C-1),
1H), 7.29 (s,1H), 3.99 (s, 6H), 3.22 (m,1H), 2.90 (m,1H),1.90 (m,1H),
13
181.9 (C-4), 154.6 (C-5), 154.4 (C-8), 154.3 (C-2), 136.8 (C-3), 121.7
1.67 (m, 1H), 1.43 (m, 2H), 1.24 (m, 16H), 0.88 (t, J ¼ 7.6 Hz, 3H);
NMR (CDCl , 100 MHz) 182.0 (C-1), 181.9 (C-4), 154.6 (C-5), 154.4
(C-8), 154.3 (C-2), 136.8 (C-3), 121.6 (C-7), 120.9 (C-6), 120.3 (C-9),
C
(
(
1
C-7), 120.8 (C-6), 120.4 (C-9), 120.1 (C-10), 56.9 (OCH
3
), 56.7
3
d
0
0
0
0
0
OCH
3
), 53.7 (C-1 ), 31.3 (C-2 ), 28.1 (C-3 ), 22.3 (C-4 ), 22.1 (C-5 ),
0
þ
0
0
3.9 (C-6 ); ESI-MS: m/z 372.9 (M þ Na) .
120.1 (C-10), 56.8 (OCH
3
), 56.7 (OCH
3
), 53.7 (C-1 ), 31.8 (C-2 ), 29.6
0
0
0
0
0
0
(
C-3 ), 29.5 (C-4 ), 29.5 (C-5 ), 29.3 (C-6 ), 29.3 (C-7 ), 29.2 (C-8 ),
0
0
0
0
5
.1.7. 2-Heptylsulfinyl-5,8-dimethoxy-1,4-naphthoquinine (3g)
It was obtained from 2g as a red solid in 46.9% yield; mp 106 C;
H NMR (CDCl , 400 MHz)
7.41 (d, J ¼ 9.6 Hz, 1H), 7.36 (d,
28.5 (C-9 ), 22.7 (C-10 ), 22.2 (C-11 ), 14.1 (C-12 ); ESI-MS: m/z 457.1
(M þ Na) .
ꢀ
þ
1
3
d
J ¼ 9.2 Hz, 1H), 7.29 (s, 1H), 3.99 (s, 6H), 3.23 (m, 1H), 2.90 (m, 1H),
5.1.13. 2-Pentadecansulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3m)
It was obtained from 2m as an orange solid in 71.6% yield; mp
1.90 (m, 1H), 1.67 (m, 1H), 1.44 (m, 2H), 1.36 (m, 2H), 1.27 (m, 4H),
1
3
ꢀ
1
0
.87 (t, J ¼ 6.8 Hz, 3H); C NMR (CDCl
3
, 100 MHz)
d
182.0 (C-1),
110 C; H NMR (CDCl
3
, 400 MHz)
d
7.41 (d, J ¼ 9.6 Hz, 1H), 7.36 (d,
181.9 (C-4), 154.5 (C-5), 154.4 (C-8), 154.3 (C-2), 136.9 (C-3), 121.6
J ¼ 9.6 Hz, 1H), 7.29 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 3.22 (m, 1H),
(
(
2
C-7), 120.6 (C-6), 120.3 (C-9), 120.3 (C-10), 56.9 (OCH
3
), 56.8
2.90 (m, 1H), 1.90 (m, 1H), 1.68 (m, 1H), 1.45 (m, 2H), 1.24 (m, 22H),
0
0
0
0
0
13
OCH
3
), 53.7 (C-1 ), 31.5 (C-2 ), 28.8 (C-3 ), 28.5 (C-4 ), 22.5 (C-5 ),
0.87 (t, J ¼ 7.6 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d 181.9 (C-1),
0
0
þ
2.2 (C-6 ), 14.0 (C-7 ); ESI-MS: m/z 386.9 (M þ Na) .
181.8 (C-4), 154.6 (C-5), 154.4 (C-8), 154.2 (C-2), 136.8 (C-3), 121.7
(
C-7), 121.0 (C-6), 120.3 (C-9), 120.2 (C-10), 56.9 (OCH
3
), 56.7
0
0
0
0
0
5
.1.8. 2-Octylsulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3h)
(OCH
3
), 53.7 (C-1 ), 31.9 (C-2 ), 29.6 (C-3 ), 29.6 (C-4 ), 29.6 (C-5 ),
ꢀ
0 0 0 0 0
It was obtained from 2h as a red solid in 63.2% yield; mp 110 C;
H NMR (CDCl , 400 MHz)
7.41 (d, J ¼ 9.2 Hz, 1H), 7.36 (d,
29.5 (C-6 ), 29.5 (C-7 ), 29.4 (C-8 ), 29.3 (C-9 ), 29.3 (C-10 ), 29.1 (C-
11 ), 28.5 (C-12 ), 22.6 (C-13 ), 22.2 (C-14 ), 14.1 (C-15 ); ESI-MS: m/z
499.1 (M þ Na) .
1
0
0
0
0
0
3
d
þ
J ¼ 9.6 Hz, 1H), 7.30 (s, 1H), 3.99 (s, 6H), 3.23 (m, 1H), 2.90 (m, 1H),
1.90 (m, 1H), 1.64 (m, 1H), 1.45 (m, 2H), 1.25 (m, 8H), 0.87 (t,
13
J ¼ 7.2 Hz, 3H); C NMR (CDCl
3
,100 MHz):
d
182.0 (C-1),181.9 (C-4),
5.1.14. 2-Octadecansulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3n)
It was obtained from 2n as an orange solid in 52.3% yield; mp
154.5 (C-5), 154.4 (C-8), 154.3 (C-2), 136.8 (C-3), 121.6 (C-7), 120.6
ꢀ
1
(
1
C-6), 120.3 (C-9), 120.3 (C-10), 56.9 (OCH
3
), 56.8 (OCH
3
), 53.7 (C-
116 C; H NMR (CDCl
3
, 400 MHz)
d
7.41 (d, J ¼ 9.6 Hz, 1H), 7.36 (d,
0
0
0
0
0
0
), 31.7 (C-2 ), 29.1 (C-3 ), 29.0 (C-4 ), 28.5 (C-5 ), 22.6 (C-6 ), 22.2
J ¼ 9.6 Hz, 1H), 7.28 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H), 3.22 (m, 1H),
0
0
þ
(
C-7 ), 14.1 (C-8 ); ESI-MS: m/z 400.8 (M þ Na) .
2.90 (m, 1H), 1.90 (m, 1H), 1.67 (m, 1H), 1.44 (m, 2H), 1.25 (m, 28H),
13
0
.87 (t, J ¼ 6.8 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d 181.9 (C-1),
5
.1.9. 2-Nonylsulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3i)
181.8 (C-4), 154.6 (C-5), 154.4 (C-8), 154.2 (C-2), 136.8 (C-3), 121.7
ꢀ
1
It was obtained from 2i as a red solid in 74% yield; mp 100 C; H
NMR (CDCl , 400 MHz)
7.42 (d, J ¼ 9.6 Hz, 1H), 7.37 (d, J ¼ 9.6 Hz,
H), 7.31 (s, 1H), 3.99 (s, 6H), 3.23 (m, 1H), 2.90 (m, 1H),1.90 (m,1H),
(C-7), 120.9 (C-6), 120.4 (C-9), 120.2 (C-10), 56.8 (OCH
3
), 56.7
0
0
0
0
0
3
d
(OCH
3
), 53.7 (C-1 ), 31.8 (C-2 ), 29.6 (C-3 ), 29.6 (C-4 ), 29.6 (C-5 ),
0 0 0 0 0
1
29.6 (C-6 ), 29.6 (C-7 ), 29.5 (C-8 ), 29.5 (C-9 ), 29.5 (C-10 ), 29.4 (C-
13
0 0 0 0 0 0
11 ), 29.3 (C-12 ), 29.3 (C-13 ), 29.1 (C-14 ), 28.5 (C-15 ), 22.6 (C-16 ),
1
.61 (m, 1H), 1.43 (m, 2H), 1.24 (m, 10H), 0.87 (t, J ¼ 7.2 Hz, 3H);
NMR (CDCl , 100 MHz) 182.0 (C-1), 181.9 (C-4), 154.6 (C-5), 154.4
C-8), 154.3 (C-2), 136.8 (C-3), 121.7 (C-7), 120.9 (C-6), 120.4 (C-9),
C
0
0
þ
3
d
22.2 (C-17 ), 14.0 (C-18 ); ESI-MS: m/z 541.0 (M þ Na) .
5.2. General procedure for the synthesis of compounds 4ae4n
To a solution of 2-alkylthio-5,8-dimethoxy1,4-naphthoquinones
(
0
0
120.4 (C-10), 56.9 (OCH
3
), 56.8 (OCH
3
), 53.7 (C-1 ), 31.8 (C-2 ), 29.3
0
0
0
0
0
0
(
C-3 ), 29.2 (C-4 ), 29.1 (C-5 ), 28.5 (C-6 ), 22.6 (C-7 ), 22.2 (C-8 ),
0
þ
14.1 (C-9 ); ESI-MS: m/z 414.8 (M þ Na) .
(2ae2n, 0.21 mmol) in chloroform (20 ml), 77% m-chloroperox-
5
.1.10. 2-Decylsulfinyl-5,8-dimethoxy-1,4-naphthouinone (3j)
ybenzoic acid (0.43 mmol) was added at room temperature, stirred,
and monitored by TLC. When the starting was disappeared, the
chloroform solution was washed with sodium hydrogen carbonate
solution, dried over sodium sulfate, and evaporated. The residue
was purified on silica gel column chromatography (HX:EA ¼ 2:1e
1:2), to give alkylsulfonyl-5,8-diemthoxy-1,4-naphthoquinones
(4ae4n).
ꢀ
1
It was obtained from 2j as a redsolid in 92.4% yield; mp 127 C; H
NMR (CDCl , 400 MHz)
7.41 (d, J ¼ 9.6 Hz, 1H), 7.36 (d, J ¼ 9.2 Hz,
H), 7.30 (s,1H), 3.99 (s, 6H), 3.22 (m,1H), 2.90 (m,1H),1.89 (m,1H),
3
d
1
13
1
.62 (m, 1H), 1.43 (m, 2H), 1.24 (m, 12H), 0.87 (t, J ¼ 7.6 Hz, 3H);
NMR (CDCl , 100 MHz) 182.0 (C-1), 181.9 (C-4), 154.6 (C-5), 154.4
C-8), 154.3 (C-2), 136.9 (C-3), 121.7 (C-7), 120.9 (C-6), 120.3 (C-9),
C
3
d
(
1
0 0
3 3
20.1 (C-10), 56.9 (OCH ), 56.8 (OCH ), 53.7 (C-1 ), 31.8 (C-2 ), 29.4
0
0
0
0
0
0
0
(
C-3 ), 29.3 (C-4 ), 29.2 (C-5 ), 29.2 (C-6 ), 28.5 (C-7 ), 22.6 (C-8 ), 22.2
5.2.1. Synthesis of 2-methylsulfonyl-5,8-dimethoxy-1,4-naphthoquin-
one (4a)
0
þ
(
C-9 ), 14.1 (C-10 ); ESI-MS: m/z 429.2 (M þ Na) .
It was obtained from 2a as a dark red solid in 46.9% yield; mp
ꢀ
1
5.1.11. 2-Undecylsulfinyl-5,8-dimethoxy-1,4-naphthoquinone (3k)
211 C; H NMR (CDCl
3
, 400 MHz)
6H), 3.37 (s, 3H); C NMR (CDCl , 100 MHz)
4), 154.4 (C-5), 154.0 (C-8), 145.5 (C-2), 139.4 (C-3), 121.3 (C-7), 121.3
d
7.49 (s, 1H), 7.41 (s, 2H), 3.99 (s,
ꢀ
13
It was obtained from 2k as a red solid in 76.5% yield; mp 119 C;
H NMR (CDCl , 400 MHz)
7.38 (d, J ¼ 9.6 Hz, 1H), 7.34 (d,
3
d
182.6 (C-1), 179.6 (C-
1
3
d