A. Boumendjel et al.
MED
1,3,5-Trihydroxy-9H-xanthen-9-one (14): A mixture of 7 (0.05 g,
0.19 mmol) and BBr3 (0.326 mL, 1.9 mmol) in CH2Cl2 was stirred at
RT for 24 h. The reaction mixture was poured onto crushed ice and
then extracted with CH2Cl2. The resulting organic layer was washed
with H2O, dried over Na2SO4, and the solvent was evaporated to
yield the desired product (dark beige powder, 0.136 g, yield 56%);
Compound 19: mp: 180–1828C; 1H NMR (400 MHz, CDCl3): d=
3.88 (s, 6H), 3.97 (s, 3H), 6.33 (s, 1H), 6.46 (s, 1H), 6.77 (s, 1H), 6.88
(d, J=9.0 Hz, 1H), 8.19 ppm (d, J=8.9 Hz, 1H); 13C NMR (75 MHz,
[D6]acetone): d=56.3, 56.3, 56.5, 93.8, 95.9, 100.5, 106.7, 113.5,
117.7, 128.5, 156.1, 160.9, 163.0, 165.2, 165.7, 173.8 ppm; MS (ESI):
m/z 287 [M+H]+; Anal. calcd for C16H14O5: C 67.13, H 4.93, found:
C 67.03, H 4.77.
1
mp: >3008C; H NMR (400 MHz, CD3OD): d=4.59 (s, 1H), 4.83 (s,
1H), 5.75-5.49 (m, 2H), 6.00 (d, J=7.4 Hz, 1H), 8.49 (s, 1H), 9.01 (s,
1H), 11.23 ppm (s, 1H); 13C NMR (75 MHz, CD3OD): d=94.9, 99.0,
103.7, 116.3, 121.4, 122.2, 125.9, 146.0, 146.9, 158.6, 164.7, 166.4,
181.6 ppm; MS (ESI): m/z 245 [M+H]+; Anal. calcd for C13H8O5: C
63.94, H 3.30, found: C 63.84, H 3.25.
3-Benzyloxy-1-hydroxy-6-methoxy-9H-xanthen-9-one (20): A mix-
ture of 9 (0.500 g, 1.9 mmol) and benzyl bromide (0.226 mL,
1.9 mmol) and K2CO3 (0.802 g, 5.8 mmol) in acetone was stirred at
1008C for 24 h. After the reaction mixture was cooled to RT, the
solvent was evaporated, H2O was added, and the solution was ex-
tracted with CH2Cl2. The resulting organic layer was washed with
H2O, dried over Na2SO4, and the solvent was evaporated to provide
xanthone 20 (orange powder, 0.112 g, yield 17%); mp: 165–1618C;
1H NMR (400 MHz, CDCl3): d=3.93 (s, 3H), 5.15 (s, 2H), 6.43 (d, J=
2.3 Hz, 1H), 6.47 (d, J=2,3 Hz, 1H), 6.83 (d, J=2.3 Hz, 1H), 6.94
(dd, J=8.9 and 2.4 Hz, 1H), 7.33-7.51 (m, 6H), 8.15 (d, J=8.9 Hz,
1H), 13.00 ppm (s, 1H); 13C NMR (75 MHz, [D6]DMSO): d=56.2,
70.0, 93.6, 97.7, 100.5, 103.6, 113.1, 113.7, 126.84, 127.9, 127.9,
128.2, 128.6, 128.6, 136.0, 157.4, 157.5, 162.6, 165.0, 165.3,
179.1 ppm; MS (ESI): m/z 349 [M+H]+; Anal. calcd for C21H16O5: C
72.41, H 4.63, found: C 72.29, H 4.55.
Compound 15 was obtained following the same procedure as that
used for the synthesis of 14. The analytical data is reported in the
Supporting Information.
1-Hydroxy-6-methoxy-3-[(3-methylbut-2-en-1-yl)oxy]-9H-xanth-
en-9-one (16) and 6-methoxy-1,3-bis[(3-methylbut-2-en-1-
yl)oxy]-9H-xanthen-9-one (17): A mixture of 9 (0.2 g, 0.78 mmol)
and 3,3-dimethyl allyl bromide (0.207 mL, 2.19 mmol) was treated
with K2CO3 (0.409 g, 2.9 mmol) in acetone and stirred at 1008C for
24 h. The reaction mixture was cooled to RT and the solvent was
evaporated. The residue was purified by column chromatography
eluted with a gradient of cyclohexane/CH2Cl2 (1:1) to CH2Cl2 to
give compound 16 as an amorphous yellow solid (0.027 g, yield
11%), followed by compound 17 as a yellow oil (0.078 g, yield
31%).
3-Benzyloxy-1,6-dimethoxy-9H-xanthen-9-one (21): A mixture of
20 (0.4 g, 1.1 mmol) and Me2SO4 (0.104 mL, 1.1 mmol) and K2CO3
(0.476 g, 3.4 mmol) in acetone was stirred at reflux for 24 h. After
the reaction mixture was cooled RT, the solvent was evaporated,
H2O was added, and the solution was extracted with CH2Cl2. The
resulting organic layer was washed with H2O, dried over Na2SO4,
and the solvent was evaporated to give derivative 21 (orange
powder, 0.338 g, yield 85%); mp: 148–1508C; 1H NMR (400 MHz,
CDCl3): d=3.88 (s, 3H), 3.95 (s, 3H), 5.13 (s, 2H), 6.41 (d, J=2.2 Hz,
1H), 6.54–6.49 (m, 1H), 6.74 (d, J=2.3 Hz, 1H), 6.84–6.91(m, 1H),
7.33–7.49 (m, 6H), 8.19 ppm (d, J=8.9 Hz, 1H); 13C NMR (75 MHz,
[D6]acetone): d=56.3, 56.5, 71.1, 94.8, 96.6, 100.5, 107.4, 113.5,
117.1, 128.51, 128.7, 128.7, 129.0, 129.5, 129.5, 137.5, 156.4, 160.7,
164.3, 164.4, 164.7, 165.2 ppm; MS (ESI): m/z 363 [M+H]+; Anal.
calcd for C22H18O5: C 72.92, H 5.01, found: C 71.03, H 5.07.
Compound 16: mp: 103–1058C; 1H NMR (400 MHz, CDCl3): d=
1.78 (s, 3H), 1.83 (s, 3H), 3.92 (s, 3H), 4.59 (d, J=6.7 Hz, 2H), 5.48-
5.51 (m, 1H), 6.33 (d, J=2.1 Hz, 1H), 6.38 (d, J=2.1 Hz, 1H), 6.81
(d, J=2.2 Hz, 1H), 6.91 (dd, J=8.9 and 2.3 Hz, 1H), 8.12 ppm (d,
J=8.9 Hz, 1H); 13C NMR (75 MHz, [D6]acetone): d=18.3, 25.8, 56.6,
66.3, 94.0, 98.3, 101.1, 103.9, 114.3, 114.8, 120.0, 127.8, 139.1, 158.6,
158.9, 164.4, 166.6, 166.8, 180.7 ppm; MS (ESI) m/z 327 [M+H]+;
Anal. calcd for C19H18O5: C 69.93, H 5.56, found: C 69.82, H 5.52.
1
Compound 17: H NMR (400 MHz, CDCl3): d=1.75–1.83 (m, 12H),
3.88 (s, 3H), 4.58 (d, J=6.7 Hz, 2H), 4.65 (d, J=6.3 Hz, 2H), 5.49-
5.53 (m, 1H), 5.62-5.65 (m, 1H), 6.34 (d, J=2.1 Hz, 1H), 6.44 (d, J=
2.1 Hz, 1H), 6.75 (d, J=2.2 Hz, 1H), 6.86 (dd, J=8.9, 2.3 Hz, 1H),
8.18 ppm (d, J=8.9 Hz, 1H); 13C NMR (75 MHz, [D6]acetone): d=
18.3, 18.4, 25.8, 25.9, 56.3, 66.1, 66.3, 66.9, 94.5, 97.5, 100.5, 107.8,
113.4, 117.8, 120.3, 120.9, 128.5, 137.5, 138.9, 157.4, 160.5, 162.0,
164.7, 165.1, 173.8 ppm; MS (ESI) m/z 395 [M+H]+; Anal. calcd for
C24H26O5: C 73.08, H 6.64, found: C 73.00, H 6.59.
N-(6,8-Dihydroxy-9-oxo-9H-xanthen-3-yl)-2,2,2-trifluoroaceta-
mide (22): The compound was obtained following the general pro-
cedure for the synthesis of xanthones using phloroglucinol
(0.126 g, 1 mmol) and 2-hydroxy-4-(2,2,2-trifluoroacetamido)benzo-
ic acid (0.25 g, 1 mmol). The later was obtained by condensation
between the trifluoroacetic anhydride and the anthranilic acid. The
product was further purified by column chromatography eluting
with CH2Cl2/EtOAc (3:7) to give compound 20 (yellow powder,
0.123 g, 35%); mp: >3008C; 1H NMR (400 MHz, [D6]DMSO): d=
6.17 (d, J=2.1 Hz, 1H), 6.37 (d, J=2.0 Hz, 1H), 7.64 (dd, J=8.7,
1.8 Hz, 1H), 7.93 (d, J=1.7 Hz, 1H), 8.08 (d, J=8.7 Hz, 1H),
12.75 ppm (s, 1H); 13C NMR (75 MHz, [D6]DMSO): d=89.8, 95.9,
104.4, 108.3, 112.0, 113.9, 114.1, 126.4, 145.4, 146.3, 148.2, 156.3 (q),
162.1, 165.0, 181.0 ppm; MS (ESI) m/z 340 [M+H]+; Anal. calcd for
C15H8F3NO5: C 53.11, H 2.38, N 4.13, found: C 53.08 H 2.33, N 4.09.
1-Hydroxy-3,6-dimethoxy-9H-xanthen-9-one (18) and 1,3,6-tri-
methoxy-9H-xanthen-9-one (19):
A
mixture of
9
(0.30 g,
1.2 mmol) and Me2SO4 (0.113 mL, 1.2 mmol) and K2CO3 (0.48 g,
3.5 mmol) in acetone was stirred at 558C for 18 h. After the reac-
tion mixture was cooled to RT, the solvent was evaporated, H2O
was added, and the resulting precipitate was filtered, washed with
H2O, and dried. The residue was purified by column chromatogra-
phy eluting with CH2Cl2 to provide compound 18 (orange powder,
yield 19%), and compound 19 (beige powder, 0.062 g, yield 31%).
6-Amino-1,3-dihydroxy-9H-xanthen-9-one (23): A mixture of 22
(0.400 g, 1.2 mmol) and K2CO3 (0.168 g, 1.2 mmol) in MeOH was
stirred at RT for 15 h. The solvent was evaporated, H2O was added,
and the solution was neutralized and extracted with EtOAc. The re-
sulting organic layer was washed with H2O, dried over Na2SO4, and
the solvent was evaporated to give compound 23 (light yellow
powder, 0.166 g, yield 57%); mp: >3008C; 1H NMR (400 MHz,
[D6]DMSO): d=6.08 (d, J=2.0 Hz, 1H), 6.25 (d, J=2.0 Hz, 1H), 6.42
1
Compound 18: mp: 87–898C; H NMR (400 MHz, CDCl3): d=3.89
(s, 3H), 3.94 (s, 3H), 6.35 (s, 1H), 6.41 (s, 1H), 6.84 (s, 1H), 6.94 (d,
J=8.9 Hz, 1H), 8.15 (d, J=8.9 Hz, 1H), 12.96 ppm (s, 1H); 13C NMR
(75 MHz, [D6]DMSO): d=55.3, 56.0, 92.4, 97.8, 101.0, 102.2, 112.7,
113.1, 126.2, 155.8, 162.0, 165.1, 166.4, 182.3 ppm; MS (ESI): m/z
273 [M+H]+; Anal. calcd for C15H12O5: C 66.18, H 4.45, found: C
66.24, H 4.42.
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemMedChem 2011, 6, 1478 – 1484