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B.-W. Li et al. / Bioorg. Med. Chem. xxx (2014) xxx–xxx
(s, 3H), 2.28 (s, 3H).
5.1.16. 4-(5-Acetoxy-7-(tert-Butoxy)-4-oxo-4H-chromen-3-
yl)phenyl acetate (17b)
5.1.11. 2-(3,4-Dihydroxyphenyl)-7-((4-fluorobenzyl)oxy)-3,5-
dihydroxy-4H-chromen-4-one (1a)
Compound 17b was prepared from 14 according to the same
procedure described for 16b, as a yellow solid. ESI-MS m/z: 411
(M+H)+.
A cold mixture of 15a (289 mg, 0.50 mmol) in NH3/MeOH
(12 mL, 0 °C) was stirred for 2 h at rt. After concentration under
reduced pressure, the residue was recrystallized with acetone to
give 1a (182 mg, 89% yield), as a yellow solid. 1H NMR (300 MHz,
CD3OD): d 7.75 (d, J = 2.1 Hz, 1H), 7.64 (dd, J = 8.6, 2.1 Hz, 1H),
7.48 (dd, J = 8.5, 5.4 Hz, 2H), 7.12 (t, J = 8.8 Hz, 2H), 6.88 (d,
J = 8.5 Hz, 1H), 6.62 (d, J = 2.1 Hz, 1H), 6.35 (d, J = 2.1 Hz, 1H),
5.12 (s, 2H). 13C NMR (125 MHz, d6-DMSO): d 176.39, 164.22,
162.40 (d, J = 244.1 Hz), 160.88, 156.44, 148.30, 147.80, 145.52,
136.52, 132.89, 130.67 (d, J = 8.4 Hz), 122.30, 120.47, 115.86 (d,
J = 21.4 Hz), 104.62, 98.47, 93.24, 69.69. EI-MS m/z: 410 (M)+. HR-
EI MS calcd for C22H15FO7 (M)+: 410.0802, found: 410.0795.
5.1.17. 7-(tert-Butoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-
chromen-4-one (7b)
Compound 7b was prepared from 17b according to the same
procedure described for 4b (28 mg, 15% yield), as a yellow solid.
1H NMR (300 MHz, CDCl3): d 12.69 (s, 1H), 7.87 (s, 1H), 7.40 (d,
J = 7.8 Hz, 2H), 6.90 (d, J = 7.8 Hz, 2H), 6.48 (d, J = 12 Hz, 1H), 5.09
(s, 1H), 1.48 (d, J = 1.4 Hz, 9H). EI-MS m/z: 326 (M) +. HR-EI MS
calcd for C19H18O5 (M)+: 326.1154, found: 326.1155.
5.1.18. 7-((4-Fluorobenzyl)oxy)-4-oxo-2-phenyl-4H-chromene-
5,6-diyl diacetate (18a)
A mixture of 11 (396 mg, 1 mmol), 4-flurobenzyl bromide
(372 lL, 3 mmol) and anhydrous K2CO3 (552 mg, 4 mmol) in ace-
5.1.12. 7-((4-Fluorobenzyl)oxy)-5-hydroxy-2-(4-
tone (250 mL) was refluxed for 24 h with stirring. The reaction
mixture was cooled down to room temperature, filtered and the
solvent was evaporated under reduced pressure to give the crude
product as a pale white solid. The solid washed with EtOAc to give
compound 18a (416 mg, 90%) as a white powder. 1H NMR
(300 MHz, CDCl3): d 7.89–7.80 (m, 2H), 7.57–7.47 (m, 2H), 7.46–
7.31 (m, 4H), 7.28–7.25 (m, 1H), 7.00 (s, 1H), 6.62–6.58 (m, 1H),
5.20 (s, 2H), 2.45 (s, 3H), 2.30 (s, 3H).
hydroxyphenyl)-4H-chromen-4-one (4a)
Compound 4a was prepared from 16a according to the same
procedure described for 1a (61 mg, 76% yield), as a yellow solid.
1H NMR (300 MHz, d6-DMSO): d 13.03 (s, 1H), 7.98 (d, J = 8.7 Hz,
2H), 7.55 (d, J = 8.7 Hz, 2H), 7.31–7.21 (m, 2H), 6.99–6.91 (m,
2H), 6.89–6.85 (m, 2H), 6.47 (d, J = 2.2 Hz, 1H), 5.23 (s, 2H). 13C
NMR (125 MHz, d6-DMSO): d 182.32, 164.51, 164.40, 163.33,
162.35 (d, J = 244.2 Hz), 161.74, 161.65, 161.38, 157.56, 132.79,
130.60 (d, J = 8.2 Hz), 128.95, 121.46, 116.40, 115.79 (d,
J = 21.4 Hz), 105.23, 103.46, 98.98, 93.91, 69.66. EI-MS m/z: 378
(M)+. HR-EI MS calcd for C22H15FO5 (M)+: 378.0904, found:
378.0903.
5.1.19. 7-(tert-Butoxy)-4-oxo-2-phenyl-4H-chromene-5,6-diyl
diacetate (18b)
A suspension of 18a (93 mg, 0.2 mmol) in MeOH (10 mL) was
treated with 10% Pd(OH)2/C (8 mg) under a flow of hydrogen until
the starting material disappeared. The reaction mixture was then
filtered on Celite and eluted with MeOH. After concentration of
the filtrate under vacuum, the residue was purified by column
chromatography on silica gel (hexanes/EtOAc = 1:1) to afford a
yellow solid. Then, from the yellow solid, the compound 18b was
prepared as a white solid according to the same procedure
described for 16b. ESI-MS m/z: 411 (M+H)+.
5.1.13. 7-((4-Fluorobenzyl)oxy)-5-hydroxy-3-(4-
hydroxyphenyl)-4H-chromen-4-one (7a)
Compound 7a was prepared from 17a according to the same
procedure described for 1a (176 mg, 91% yield), as a yellow solid.
1H NMR (300 MHz, d6-DMSO): d 12.73 (s, 1H), 9.68 (s, 1H), 8.42
(s, 1H), 7.59–7.50 (m, 2H), 7.41 (d, J = 8.7 Hz, 2H), 7.30–7.21 (m,
2H), 6.83 (d, J = 8.7 Hz, 2H), 6.76 (d, J = 2.3 Hz, 1H), 6.51 (d,
J = 2.2 Hz, 1H), 5.20 (s, 2H). 13C NMR (100 MHz, d6-DMSO): d
207.01, 180.88, 164.54, 162.41 (d, J = 244.1 Hz), 162.23, 157.92
(d, J = 7.7 Hz), 154.93, 132.75, 130.78 (d, J = 8.4 Hz), 122.97,
121.48, 115.85 (d, J = 21.4 Hz), 106.00, 99.12, 93.74, 67.05, 31.16.
EI-MS m/z: 378 (M)+. HR-EI MS calcd for C22H15FO5 (M)+:
378.0904, found: 378.0903.
5.1.20. 7-((4-Fluorobenzyl)oxy)-5,6-dihydroxy-2-phenyl-4H-
chromen-4-one (2a)
A cold mixture of 18a (520 mg, 1.12 mmol) in NH3/MeOH
(12 mL) was stirred at room temperature for 2 h. After concentra-
tion under reduced pressure, the residue was recrystallized with
acetone to afford 2a (385 mg, 91% yield) as a yellow solid. 1H
NMR (300 MHz, CDCl3): d 7.91–7.85 (m, 2H), 7.57–7.41 (m, 5H),
7.15–7.06 (m, 2H), 6.69 (m, 1H), 6.64 (s, 1H), 5.21 (s, 2H). 13C
5.1.14. 4-(5-Acetoxy-7-(tert-Butoxy)-4-oxo-4H-chromen-2-
yl)phenyl acetate (16b)
NMR (125 MHz, d6-DMSO):
d
182.81, 163.69, 162.37 (d,
To a suspension of 13 (130 mg, 0.4 mmol), Mg(ClO4)2 (12 mg,
0.06 mmol) in DCM was added Boc2O (283 mg, 1.3 mmol). The
mixture was stirred for 24 h at 70 °C. The resulting mixture was
diluted with 200 mL of DCM and washed with water (100 mL).
The residue obtained after evaporation of the solvent was used in
the next step without further purification. ESI-MS m/z: 411 (M+H)+.
J = 243.8 Hz), 153.91, 150.10, 146.93, 132.98, 132.46, 131.31,
130.88, 130.54 (d, J = 8.3 Hz), 129.62, 126.80, 115.77 (d,
J = 21.4 Hz), 105.90, 105.21, 93.00, 69.97. EI-MS m/z: 378 (M)+.
HR-EI MS calcd for C22H15FO5 (M)+: 378.0904, found: 378.0899.
5.1.21. 7-(tert-Butoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one
(5a)
5.1.15. 7-(tert-Butoxy)-5-hydroxy-2-(4-hydroxyphenyl)-4H-
chromen-4-one (4b)
To a solution of 5 (510 mg, 2 mmol) in DMF (10 mL) were added
K2CO3 (276 mg, 2 mmol) and 4-flurobenzyl bromide (372 lL,
A cold mixture of 16b (230 mg, 0.56 mmol) in NH3/MeOH
(12 mL, 0 °C) was stirred for 2 h at rt. The residue obtained after
evaporation of the solvent was purified by flash column chroma-
tography using hexanes/EtOAc (4:1) as eluent to afford 4b
3 mmol) under argon. The reaction mixture was agitated vigor-
ously at room temperature for 12 h. The mixture was diluted with
EtOAc and washed with water. The organic phase was evaporated
under reduced pressure to give the crude product, which was puri-
fied by column chromatography on silica gel (hexanes/EtOAc = 4:1)
to afford 5a (707 mg, 95% yield) as a yellow solid. 1H NMR
(300 MHz, CDCl3): d 12.76 (s, 1H), 7.89 (m, 2H), 7.59–7.49 (m,
3H), 7.46–7.36 (m, 2H), 7.10 (m, 2H), 6.68 (d, J = 2.5 Hz, 1H), 6.57
(d, J = 2.5 Hz, 1H), 6.45 (s, 1H), 5.10 (s, 2H). 13C NMR (125 MHz,
(26 mg, 16% yield). 1H NMR (300 MHz, CD3OD):
d 7.91 (d,
J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 6.65 (s, 1H), 6.46 (d,
J = 2.1 Hz, 1H), 6.23 (d, J = 2.0 Hz, 1H), 1.43 (s, 9H). EI-MS m/z:
326 (M) +. HR-EI MS calcd for C19H18O5 (M)+: 326.1154, found:
326.1152.