Substituted Anthraquinones against Brugia malayi
Journal of Medicinal Chemistry, 2005, Vol. 48, No. 8 2829
reaction mixture was cooled in an ice bath. Dimethyl sulfate
(0.2 mmol) was added and allowed to stir for several hours at
room temperature. The solvent was evaporated under vacuum,
and the residue was dissolved in water and extracted with
ethyl acetate. The resulting residue was purified by silica
MPLC using 20% ethyl acetate in hexane as the mobile phase.
1,2-Dihydroxyanthraquinone (A). Yield: 55%. Mp: 173-
174 °C. UV λmax (CH3OH) (log ꢀ): 205 (4.47), 246 (4.6), 275
(C-1), 151.14 (C-2), 136.66 (C-7), 133.14 (C-8a), 124.63 (C-6),
123.16 (C-4a), 121.48 (C-9a), 120.74 (C-4), 118.83 (C-8), 116.20
(C-3), 115.92 (C-10a). FABMS: m/z 257 (11), 256 (6), 246 (5),
232 (7), 209 (3). HRFAB: m/z 257.0449 [MH+].
1,2,8-Trihydroxyanthraquinone (I). Yield: 10%. Mp:
234-235 °C. UV λmax (CH3OH) (log ꢀ): 288 (4.90), 347 (4.29)
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nm. H NMR (DMSO): δ 7.26 (d, 1H, J ) 8.5, H3), 7.57 (dd,
1H, J ) 8.5, 1, H5), 7.68 (d, 1H, J ) 8, H4), 7.21 (dd, 1H, J )
7.5, 1, H7), 7.83 (t, 1H, J ) 8, H6). 13C NMR (DMSO): δ 192.59
(C-9), 180.07 (C-10), 161.34 (C-8), 152.93 (C-1), 150.57 (C-2),
137.49 (C-6), 133.83 (C-10a), 123.78 (C-7), 123.73 (C-8a), 121.42
(C-4a), 120.98 (C-4), 119.04 (C-5), 116.18 (C-3), 116.09 (C-9a).
FABMS: m/z 257 (40), 256 (18), 246 (4), 232 (19), 209 (8).
HRFAB: m/z 257.0449 [MH+].
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(4.4), 431 (3.7) nm. H NMR (DMSO): δ 7.27 (d, 1H, J ) 8.5,
H3), 7.70 (d, 1H, J ) 8.5, H4), 7.95 (m, 2H, H6, H7), 8.23 (m,
2H, H5, H8). 13C NMR (DMSO): δ 190.25 (C-9), 182.03 (C-
10), 154.2 (C-1), 152.28 (C-2), 136.57 (C-10a), 135.51 (C-8a),
135.04 (C-6), 134.16 (C-7), 128.59 (C-5), 127.95 (C-8), 125.26
(C-9a), 122.70 (C-3), 122.31 (C-4a), 117.73 (C-4). FABMS: m/z
241 (25), 240 (10), 232 (8), 209 (4). HRFAB: m/z 241.0502
[MH+].
1,2-Dihydroxy-3-methylanthraquinone (B). Yield: 50%.
Mp: 224-225 °C. UV λmax (CH3OH) (log ꢀ): 206 (4.46), 245
(4.36), 270 (4.39), 280 (4.39), 417 (3.57) nm. 1H NMR
(DMSO): δ 2.32 (s, 3H, 3-CH3), 7.61 (s, 1H, H4), 7.94 (m, 2H,
H6, H7), 8.21 (m, 2H, H5, H8). 13C NMR (DMSO): δ 189.87
(C-9), 182.17 (C-10), 151.61 (C-1), 151.11 (C-2), 135.48 (C-3),
134.99 (C-10a), 134.29 (C-8a), 133.48 (C-6), 128.18 (C-5), 127.82
(C-8), 124.57 (C-10), 124.02 (C-4a), 115.96 (C-4), 17.90 (C-11).
FABMS: m/z 255 (15), 254 (7), 232 (19), 209 (4). HRFAB: m/z
255.0655 [MH+].
1,2,8-Trihydroxy-3-methylanthraquinone (J). Yield:
30%. Mp: 239-240 °C. UV λmax (CH3OH) (log ꢀ): 256 (4.01),
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427 (3.69) nm. H NMR (DMSO): δ 2.24 (s, 3H, 3-CH3), 7.32
(d, 1H, J ) 8.5 Hz, H7), 7.54 (1H, s, H4), 7.67 (d, 1H, J ) 7.5
Hz, H5), 7.74 (t, 1H, J ) 7.5, H6). 13C NMR (DMSO): δ 16.45
(C-11), 114.35 (C-9a), 115.94 (C-8a), 119.05 (C-5), 122.87 (C-
4), 123.11 (C-4a), 123.73 (C-7), 132.32 (C-3), 132.75 (C-10a),
137.40 (C-6), 149.38 (C-1), 150.27 (C-2), 161.26 (C-8), 180.19
(C-10), 192.26 (C-9). FABMS: m/z 271 (7), 270 (2), 232 (24),
214 (5). HRFAB: m/z 271.0606 [MH+].
1-Methyl-2,3,8-trihydroxy anthraquinone (K). Yield:
15%. Mp: 304-305 °C (dec). UV λmax (CH3OH) (log ꢀ): 288
(4.90), 347 (4.29); 1H NMR (DMSO): δ 2.65 (s, 3H, 1-CH3),
7.19 (d, 1H, J ) 8.5 Hz, H7), 7.60 (s, 1H, H4), 7.63 (d, 1H, J
) 7.5 Hz, H5), 7.73 (t, 1H, J ) 8, H6). 13C NMR (DMSO): δ
13.93 (C-11), 112.18 (C-4), 117.43 (C-9a), 118.65 (C-5), 124.51
(C-4a), 124.83 (C-7), 128.42 (C-8a), 129.39 (C-3), 133.39 (C-
10a), 136.63 (C-6), 150.38 (C-2), 150.90 (C-1), 162.10 (C-8),
182.14 (C-10), 191.05 (C-9). FABMS: m/z 271 (15), 256 (7),
232 (30), 214 (4). HRFAB: m/z 271.0606 [MH+].
1,3,5-Trihydroxyanthraquinone (L). Yield: 35%. Mp:
284-286 °C (dec). UV λmax (CH3OH) (log ꢀ): 268 (4.70), 426
(4.43) nm. 1H NMR (DMSO): δ 6.58 (d, 1H, 2.5 Hz, H2), 7.14
(d, 1H, 2.5 Hz, H4), 7.33 (dd, 1H, J ) 8.5, 1 Hz, H6), 7.68 (dd,
1H, J ) 7.5 Hz, 1 Hz, H8), 7.78 (t, 1H, J ) 8.0, H7). 13C NMR
(DMSO): δ 108.07 (C-2), 108.37 (C-4), 109.23 (C-9a), 115.67
(C-10a), 118.68 (C-8), 124.0 (C-6), 133.2 (C-4a), 134.64 (C-8a),
137.33 (C-7), 161.65 (C-3), 164.87 (C-1), 165.49 (C-5) 185.09
(C-10), 187.34 (C-9). FABMS: m/z 257 (20), 256 (7), 246 (4),
232 (21), 209 (4). HRFAB: m/z 257.0451 [MH+].
1-Methyl-2,3-dihydroxyanthraquinone (C). Yield: 30%.
Mp: 297-299 °C (dec). UV λmax (CH3OH) (log ꢀ): 255 (3.89),
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364 (3.48) nm. H NMR (DMSO): δ 2.63 (s, 3H, 1-CH3), 7.61
(s, 1H, H4), 7.85 (m, 2H, H6, H7), 8.10 (m, 2H, H5, H8). 13C
NMR (DMSO): δ 183.76 (C-9), 182.07 (C-10), 149.64 (C-2),
149.39 (C-3), 134.65 (C-1), 133.89 (C-10a), 132.24 (C-8a), 128.00
(C-6), 127.48 (C-7), 126.55 (C-5), 125.74 (C-8), 124.90 (C-9a),
111.12 (C-4a), 110.96 (C-4), 13.61 (C-11). FABMS: m/z 255
(90), 254 (37), 232 (20), 209 (3). HRFAB: m/z 255.0658 [MH+].
1,3-Dihydroxyanthraquinone (D). Yield: 60%. Mp: 207-
208 °C. UV λmax (CH3OH) (log ꢀ): 211 (4.18), 282 (3.89), 311
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(3.69), 410 (3.41) nm. H NMR (DMSO): δ 5.73 (s, 1H, H2),
6.59 (s, 1H, H4), 7.72 (t, 1H, J ) 7.5, H6), 7.83 (t, 1H, J ) 7.5,
H7), 8.07 (d, 1H, J ) 7.5, H8), 8.13 (d, 1H, J ) 8.0, H7).
FABMS: m/z 241 (12), 240 (3), 232 (16), 209 (7). HRFAB: m/z
241.0500 [MH+].
1,4-Dihydroxyanthraquinone (E). Yield: 80%. Mp: 195-
196 °C. UV λmax (CH3OH) (log ꢀ): 206 (4.51), 223, (4.54) 248
(4.64), 278 (4.20), 479 (4.02) nm. 1H NMR (DMSO): δ 7.47 (s,
2H, H2, H3), 8.01 (m, 2H, H6, H7), 8.30 (m, 2H, H5, H8). 13C
NMR (DMSO): δ 1187.40 (C-9, C-10), 157.40 (C-1, C-4), 135.77
(C-10a, 8a), 133.61 (C-6, C-7), 133.04 (C-5, C-8), 127.38 (C-4a,
C-9a), 113.40 (C-2, C-3). FABMS: m/z 241 (16), 240 (10), 232
(12), 209 (6). HRFAB: m/z 241.0500 [MH+].
1,2,3-Trihydroxy anthraquinone (F). Yield: 75%. Mp:
282-284 °C. UV λmax (CH3OH) (log ꢀ): 207 (4.59), 243 (4.39),
283 (4.49), 410 (3.71) nm. 1H NMR (DMSO): δ 7.29 (s, 1H,
H4), 7.91 (m, 2H, H6, H7), 8.18 (m, 2H, H5, H8): 13C NMR
(DMSO): δ 187.63 (C-9), 181.67 (C-10), 152.72 (C-1), 152.48
(C-2), 139.65 (C-3), 135.22 (C-10a), 134.79 (C-8a), 133.94 (C-
6), 133.77 (C-7), 127.30 (C-8), 126.94 (C-5), 125.37 (C-9a),
111.03 (C-4a), 109.52 (C-4). FABMS: m/z 257 (11), 256 (6),
232 (7), 209 (3). HRFAB: m/z 257.0449 [MH+].
2,3,8-Trihydroxyanthraquinone (G). Yield: 30%. Mp:
302-304 °C (dec). 1H NMR (DMSO): δ 7.28 (dd, 1H, J ) 8.0,
1.0, H7), 7.47 (s, 1H, H2), 7.51 (s, 1H, H1), 7.61 (dd, 1H, J )
7.5, 1.0, H5), 7.71 (t, 1H, J ) 8.0, H6). 13C NMR (DMSO): δ
187.69 (C-9), 181.05 (C-10), 161.32 (C-8), 152.45 (C-2), 151.71
(C-3), 136.63 (C-6), 133.46 (C-10a), 127.14 (C-8a), 126.15 (C-
9a), 123.66 (C-7), 118.72 (C-5), 115.78 (C-4a), 113.21 (C-1),
112.66 (C-4). FABMS: m/z 257 (4), 256 (3), 246 (6), 232 (10),
209 (5). HRFAB: m/z 257.0449 [MH+].
1,2,5-Trihydroxyanthraquinone (H). Yield: 10%. Mp:
263-264 °C. UV λmax(CH3OH) (log ꢀ): 255 (4.56), 288 (4.35),
444 (4.08) nm. 1H NMR (DMSO): δ 7.28 (d, 1H, J ) 8.5, H2),
7.41 (dd, 1H, J ) 8.5, 1.5, H7), 7.54 (d, 1H, J ) 8.5, H3), 7.79
(dd, 1H, J ) 7.5, 1.5, H5), 7.83 (t, 1H, J ) 8, H6). 13C NMR
(DMSO): δ 188.04 (C-9), 186.57 (C-10), 161.70 (C-5), 153.61
1,4,8-Trihydroxyanthraquinone (M). Yield: 55%. Mp:
254-256 °C (dec). UV λmax (CH3OH) (log ꢀ): 283 (3.44), 488
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(3.45) 573 (2.75) nm. H NMR (DMSO): δ 7.41 (dd, 1H, J )
8.0, 1.5 Hz, H7), 7.45 (d, 2H, H2, H3), 7.80 (dd, 1H, J ) 7.5,
1.0 Hz, H6), 7.84 (t, 1H, J ) 8.0, H6). FABMS: m/z 257 (10),
256 (8), 246 (4), 232 (16), 209 (4). HRFAB: m/z 257.0449
[MH+].
1,2,3,5-Tetrahydroxyanthraquinone (N). Yield: 50%.
Mp: 278-279 °C (dec). 1H NMR (DMSO): δ 7.32 (s, 1H, H4),
7.35 (dd, 1H, J ) 7.0, 1.5 Hz, H6), 7.73 (dd, 1H, J ) 7.5 Hz,
1.5 Hz, H8), 7.88 (t, 1H, J ) 8.0, H6). 13C NMR (DMSO): δ
108.89 (C-4), 110.33 (C-9a), 115.67 (C-10a), 118.62 (C-8), 124.02
(C-4a), 124.17 (C-6), 133.29 (C-8a), 136.74 (C-8), 139.69 (C-3),
151.87 (C-2), 152.06 (C-1), 161.56 (C-5), 186.20 (C-10), 186.83
(C-9). FABMS: m/z 273 (20), 272 (10), 232 (10), 209 (4).
HRFAB: m/z 273.0398 [MH+].
1-Hydroxy-2-methoxy-3-methylanthraquinone (O).
Yield: 80%. Mp: 154-155 °C. UV λmax (CH3OH) (log ꢀ): 261
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(4.69), 337 (3.92) nm. H NMR (CDCl3): δ 8.27 (m, 2H, H5,
H8), 7.79 (m, 2H, H6, H7) 7.67 (s, 1H, H4), 4.02 (s, 3H, OCH3),
2.39 (s, 3H, 3-CH3). 13C NMR (CDCl3): δ δ 17.03 (3-CH3), 60.64
(2-OCH3), 115.91 (C-4), 122.55 (C-4a), 127.02 (C-9a), 127.61
(C-8), 127.85 (C-5), 133.58 (C-7), 133.93 (C-6), 134.17 (C-8a),
134.85 (C-10a), 140.22 (C-3), 152.14 (C-2), 155.84 (C-1), 182.30
(C-10), 188.99 (C-9). FABMS: m/z 269 (8), 268 (2), 241 (2).
HRFAB: m/z 269.0813 [MH+].
1,2-Dimethoxy-3-methylanthraquinone (P). Yield: 75%.
Mp: 127-128 °C. UV λmax (CH3OH) (log ꢀ): 263 (4.50), 409
(3.82) nm. 1H NMR (CDCl3): δ 8.26 (m, 2H, H5, H8), 7.77 (m,
2H, H6, H7) 7.99 (s, 1H, H4), 4.06 (s, 3H, 2-OCH3), 3.99 (s,