H.-W. Xu et al. / Bioorg. Med. Chem. Lett. 23 (2013) 737–739
6. (a) Knight, D. W.; Pattenden, G. J. Chem. Soc., Chem. Commun. 1975, 876; (b)
739
16. Preparation of 5-benzylidene-4-methoxy-3-phenylfuran-2(5H)-one (6). To
a
cooled (0 °C) solution of 5 (1.48, 0.005 mol) in dry THF (15 ml) was added
paratoluensulfonyl chloride (1.91 g, 0.01 mol) and DMAP (0.183 g, 0.0015 mol).
Triethylamine (0.506 g, 0.005 mol) was introduced into the reaction mixture at
the same temperature. Then the mixture was allowed to stir for 20 min. The
reaction mixture was warmed to room temperature and stirred for 2 h. Then
the mixture was heated at 90 °C for 10 h. After the reaction was complete
(monitored by TLC), the solvent was removed under reduced pressure and H2O
(15 ml) was added. The reaction mixture was extracted with EtOAc (3 Â 10 ml)
and the organic extracts were washed with water (3 Â 10 mL) and brine
(3 Â 10 mL) respectively. The combined organic extracts dried (Na2SO4),
filtered and the solvent removed in vacuo. 6 (1.22 g, 87.6%) was obtained as
a yellow solid.
Begley, M. J.; Knight, D. W.; Pattenden, G. Tetrahedron Lett. 1976, 17, 131; (c)
Knight, D. W.; Pattenden, G. J. Chem. Soc., Chem. Commun. 1976, 635; (d) Knight,
D. W.; Pattenden, G. J. Chem. Soc., Perkin Trans. 1 1979, 62; (e) Knight, D. W.;
Pattenden, G. J. Chem. Soc. Perkin Trans. 1 1979, 70; (f) Pattenden, G.; Turvill, M.
W.; Chorlton, A. P. J. Chem. Soc. Perkin Trans. 1 1991, 10, 2357.
7. Jerris, P. J.; Wovkulich, P. M.; Smith, A. B. Tetrahedron Lett. 1979, 20, 4517.
8. (a) Ramage, R.; Griffiths, G. J.; Shutt, F. E.; Sweeney, J. N. A. J. Chem. Soc., Perkin
Trans. 1 1984, 1531; (b) Ramage, R.; Griffiths, G. J.; Shutt, F. E.; Sweeney, J. N. A.
J. Chem. Soc. Perkin Trans. 1 1984, 1539.
9. Gill, M.; Kiefel, M. J.; Lally, D. A.; Ten, A. Aust. J. Chem. 1990, 43, 1497.
10. (a) Kaczybura, N.; Brückner, R. Synthesis 2007, 118; (b) Bernier, D.; Moser, F.;
Brückner, R. Synthesis 2007, 2240; (c) Bernier, D.; Brückner, R. Synthesis 2007,
2249.
11. Nadal, B.; Rouleau, J.; Besnard, H.; Thuéry, P.; Le Gall, T. Tetrahedron 2011, 67,
2605.
12. Xu, H. W.; Wang, J. F.; Liu, G. Z.; Hong, G. F.; Liu, H. M. Org. Biomol. Chem. 2007,
5, 1247.
13. Preparation of 4-hydroxy-3-phenyl-5-furan-2(5H)-one (2). To a stirred solution
of 4-fluorophenylacetic acid (4.08 g, 0.03 mol) in THF (20 ml) was added
triethylamine (4.55 g, 0.045 mol) and ethyl chloroacetate (5.51 g, 0.045 mol).
The mixture was refluxed for 8 h. After the reaction was complete (monitored
by TLC), the reaction mixture was cooled to room temperature and filtered
17. Preparation of pulvinone (1). To a stirred solution of 6 (1.39 g, 0.005 mol) in
acetonitrile (10 ml) was added lithium bromide (646 mg, 0.005 mol). The
mixture was heated at 120 °C. After the reaction was complete (monitored
by TLC) the solvent was removed under reduced pressure and H2O (10 ml)
was added. The reaction mixture was extracted with dichloromethane
(3 Â 10 ml) and the combined organic extracts dried (Na2SO4), filtered and
the solvent removed in vacuo. The residue obtained was purified by silica
gel column chromatography with petroleum ether: EtOAc (3:1) as an eluent
to give 1 (1.13 g, 85.6%) as a yellow solid. 1H NMR (400 MHz, Acetone-d6) d:
8.32 (d, J = 7.6 Hz, 2H, ArH), 7.78 (d, J = 7.6 Hz, 2H, ArH), 7.39 (q, J = 7.2 Hz,
4H, ArH), 7.33–7.27 (m, 1H, ArH), 7.20 (t, J = 7.3 Hz, 1H, ArH), 6.87 (s, 1H,
CH). 13C NMR (100 MHz, Acetone-d6) d: 171.39, 169.90, 145.51, 134.26,
132.69, 130.06, 128.56, 127.82, 127.77, 127.61, 126.87, 126.46, 125.39,
105.29, 96.82.
through
a sintered funnel. Then the filter cake was washed with THF
(3 Â 10 ml). The solvent was removed under reduced pressure and yellow oil
was obtained. To a cooled (0 °C) solution of this yellow oil obtained above in
DMF (20 ml) was added potassium t-butoxide (6.73 g, 0.06 mol) slowly and the
solution was stirred for 30 min. Then the reaction mixture was warmed to
room temperature and stirred at the same temperature for 5 h. After the
reaction was complete (monitored by TLC), it was diluted by addition of water
(20 ml) and its pH was adjusted to 3 by addition of diluted hydrochloric acid.
Finally, a great amount of white solid precipitated from the solution after
addition of water (150 ml). The mixture was filtered and the filter cake was
washed with H2O (3 Â 10 ml). 2 (4.93 g, 93.5%) was obtained as a white solid.
14. Preparation of 4-methoxyl-3-phenyl-5-furan-2(5H)-one (4). To a stirred solution
of 2 (3.52 g, 0.02 mol) in acetone (25 ml) was added potassium carbonate
(3.86 g, 0.028 mol). Dimethyl sulphate (3.02 g, 0.024 mol) in acetone (5 ml)
was added dropwise over a period of 30 min under N2 atmosphere. The
mixture was stirred at room temperature for 8–10 h. After the reaction was
complete (monitored by TLC), H2O (30 ml) was added and its pH was adjusted
to 3 by addition of diluted hydrochloric acid. The solvent was removed under
reduced pressure. The mixture was filtered and 4 (3.29 g, 90.1%) was obtained
as a slightly yellow solid.
18. NMR data of 7a. 1H NMR (400 MHz, CDCl3) d: 7.45–7.33 (m, 2H, ArH), 7.26–7.15
(m, 2H, ArH), 7.15–7.03 (m, 2H, ArH), 6.95 (t, J = 8.7 Hz, 1H, ArH), 5.05 (dd,
J = 7.0, 2.4 Hz, 1H, CH), 5.01 (d, J = 2.5 Hz, 1H, CH), 3.93–3.86 (m, 4H, CH2), 3.81
(s, 3H, OCH3), 3.17–3.05 (m, 4H, CH2). 13C NMR (100 MHz, CDCl3) d: 172.41,
171.73, 163.85, 161.38, 156.65, 154.19, 140.20, 140.12, 133.53, 133.47, 131.96,
131.88, 125.27, 125.24, 122.85, 118.56, 118.53, 115.41, 114.86, 114.64, 104.97,
79.78, 71.85, 66.92, 60.64, 50.77, 50.74.
19. NMR data of 8a. 1H NMR (400 MHz, CDCl3) d: 7.67–7.58 (m, 4H, ArH), 7.53 (dd,
J = 8.7, 5.4 Hz, 2H, ArH), 7.15 (t, J = 8.6 Hz, 1H, ArH), 6.25 (s, 1H, CH), 3.93–3.88
(m, 4H, CH2), 3.87 (s, 3H, OCH3), 3.19 (m, 4H, CH2). 13C NMR (100 MHz, CDCl3)
d:166.25, 165.52, 156.15, 144.87, 143.99, 131.32, 131.24, 130.88, 130.80,
127.94, 127.19, 118.45, 118.26, 118.22, 118.03, 117.85, 115.94, 115.73, 110.61,
66.85, 66.80, 50.55, 50.52, 50.34, 50.30.
20. General procedure for antimicrobial activity. Antibacterial activity was
determined using the broth microdilution method according to the National
Committee for Clinical Laboratory Standards (NCCLS). Bacterial species were
grown in Luria broth medium (RPMI 1640 medium for fungi) until exponential
growth was achieved. Tests were performed in a 96-well microtiter plate. All
the compounds were dissolved in dimethyl sulfoxide (DMSO) at an initial
15. Preparation of 5-(hydroxyl(phenyl)methyl)-4-methoxy-3-phenylfuran-2(5H)-one
(5). To a stirred solution of 4 (3.80 g, 0.02 mol) in methanol (25 ml) was added
potassium carbonate (3.86 g, 0.028 mol) and benzaldehyde (2.54 g, 0.024 mol).
The mixture was stirred at room temperature. After the reaction was complete
(monitored by TLC), the solvent was removed under reduced pressure. H2O
concentration of 5120
medium. A series of concentrations ranging from 1 to 128
volume of 200 l in plate was obtained by two-fold dilutions. Each well except
l
g/ml and the solutions were diluted with the test
l
g/ml to a final
(15 ml) was added and its pH was adjusted to
3
by addition of diluted
l
hydrochloric acid. The reaction mixture was extracted with EtOAc (3 Â 10 ml)
and the combined organic extracts dried (Na2SO4), filtered and the solvent
removed in vacuo. The residue obtained was purified by silica gel column
chromatography with petroleum ether: EtOAc (2:1) as an eluent to give 5
(4.47 g, 75.5%) as a white solid
for the blank well was inoculated with the test bacteria and incubated at 37 °C
for 24 h. The plates were read using ELIASA at OD492. The MIC50 is the lowest
concentration of compound that inhibits growth to half the OD of the non-
treated control.