Algicidal Activity of Stilbene Analogues
J. Agric. Food Chem., Vol. 56, No. 19, 2008 9141
Figure 2. Chemical structures of stibenes with Z-configuration.
1H, J ) 12 Hz), 4.28 (dd, 1 H, J1,2 ) 4 Hz, J1,3 ) 4 Hz), 5.07 (d, 1H,
J ) 8 Hz), 5.15 (t, 1H, J ) 8 Hz), 4.26 (m, 2H), 6.37 (s, 1H), 6.63 (s,
2H), 6.96 (m, 5H), 7.42 (d, 2H, J ) 8 Hz). 13C NMR (CDCl3, 100
MHz): δ 20.6 (4C), 55.3 (2C), 61.9, 68.2, 71.1, 72, 72.6, 98.9, 104.4
(2C), 117.1 (2C), 127.7 (2C), 128.1, 132.5, 139.2, 156.4 (2C), 160.9
(4C), 169.3, 169.4, 170.6.
Figure 1. Chemical structures of stibenes with E-configuration and
compound 11.
(E)-2-[4-(3,5-Dimethoxystyryl)phenoxy]-6-(hydroxymethyl)tetrahy-
dro-2H-pyran-3,4,5-triol (19). To a solution of 18 (100 mg, 0.17 mmol)
in methanol (MeOH) (20 mL) was added 10 mL of 0.2 M of methanolic
sodium methoxide (NaOMe) (18) (Scheme 1). The reaction was stirred
for 2 h at room temperature, and Dowex 50W-X8 (H+) was added
until neutral pH was reached. The resin was filtered, and the solvent
was removed. The crude mixture was purified by column chromatog-
raphy eluting with chloroform/methanol (98:2) and gave 46 mg of 19
(27% yield). 1H NMR (DMSO-d6, 400 MHz): δ 3.14 (m, 1H), 3.23
(m, 2H), 3.32 (s, 1H), 3.44 (m, 1H), 3.66 (m, 1H), 3.74 (s, 6H), 4.57
(s, 1H), 4.87 (d, 1H, J ) 8 Hz), 5.02 (s, 1H), 5.09 (s, 1H), 5.31 (s,
1H), 6.37 (s, 1H), 6.72 (s, 2H), 7.02 (m, 3H), 7.20 (d, 1H, J ) 16 Hz),
7.50 (d, 2H, J ) 8 Hz). 13C NMR (DMSO-d6, 100 MHz): δ 60.6 (2C),
66.1, 75.1, 78.7, 82, 82.5, 105, 105.7, 109.7 (2C), 121.8 (2C), 132.1,
133.1 (2C), 133.1, 136.1, 144.7, 162.5, 166 (2C). Positive ion ESI-
HRMS: calcd for C22H26NaO8 [M + Na]+, 441.15254; found, 441.15252.
General Procedure for the Synthesis of Compounds 25a,b and 28a,b.
Aryl aldehyde, potassium hydroxide (KOH) (102 mg, 1.81 mmol), and
18 crown-6 were added to a solution of phosphonium salt 20 in
dichloromethane (DCM) (19) (Scheme 2). The reaction was stirred at
room temperature for 12 h. The reaction was poured into water and
extracted with ethyl acetate (3 × 10 mL). The organic phase was
combined and dried over MgSO4 and concentrated under reduced
pressure. The crude product was purified through flash chromatography
eluting with hexanes/ethyl acetate (98:2).
During the past decade, we have evaluated numerous natural
and natural-based compounds to discover alternatives to the
currently available algicides. A wide variety of chemical
compounds and plant and marine extracts have undergone
evaluation using a microplate bioassay in the laboratory as the
first stage in the discovery process. Quinones are one group of
compounds that were evaluated early in the research program,
and they have provided several promising leads for subsequent
efficacy testing in catfish aquaculture ponds (1).
The stilbenes are known for their wide range of biological
activities including antioxidant (7), anti-inflammatory (8),
antileukemic (9), antibacterial (10), antifungal (11), antiplatelet
aggregation (12), vasodilator (13), and antitumor (14) activities.
Stilbenes are produced in plants in response to fungal attacks
and are involved in the defense mechanism of plants.
Although previous research (15, 16) has found that certain
types of stilbenes are toxic toward the coccoid cyanobacterium
Anacystis aeruginosa (Zanardini) Drouet & Daily and the
filamentous cyanobacterium Gloeotrichia echinulata (Smith)
P.G. Richter at test concentrations of 1-200 mg/L, stilbenes
have not been previously evaluated for selective toxicity toward
the planktonic MIB producer O. perornata. In this report, the
algicidal activities of stilbene analogues toward the MIB-
producing O. perornata and a species of green algae were
evaluated.
1-(4-Chlorostyryl)-3,5-dimethoxybenzene (25a,b). The reaction of
(3,5-dimethoxybenzyl)triphenylphosphonium 20 (300 mg, 0.6 mmol)
and 4-chlorobenzaldehyde 21 (85 mg, 0.6 mmol) afforded 25a,b.
1
Compound 25a, 53 mg. H NMR (CDCl3, 400 MHz): δ 3.83 (s, 6H),
6.41 (s, 1H), 6.66 (s, 2H), 7.01 (s, 2H), 7.32 (d, 2H, J ) 8 Hz), 7.42
(d, 2H, J ) 8 Hz). 13C NMR (CDCl3, 100 MHz): δ 55.6 (2C), 100.3,
104.8 (2C), 127.9 (2C), 128, 129 (2C), 129.5, 133.5, 135.8, 139.2, 161.2
(2C). Positive ion ESI-HRMS: calcd for C16H16O2Cl [M + H]+,
275.0839; found, 275.0846. Compound 25b, 50 mg. 1H NMR (CDCl3,
400 MHz): δ 3.68 (6H), 6.36 (s, 1H), 6.40 (s, 2H), 6.55 (dd, 2H, J1,2
) 8 Hz, J1,3 ) 4 Hz), 7.21 (s, 4H). 13C NMR (CDCl3, 100 MHz): δ
55.4 (2C), 100.0, 106.8 (2C), 128.5 (2C), 129.5, 130.5 (2C), 131.1,
133.0, 135.8, 138.9, 160.8 (2C). Positive ion ESI-HRMS: calcd for
C16H16O2Cl [M + H]+, 275.0839; found, 275.0834.
MATERIALS AND METHODS
Preparation and Synthesis of Stilbene Analogues. The synthesis
of compounds 1-14 and 17 (Figures 1 and 2) has been described
previously (17). Resveratrol (16) was purchased from Sigma-Aldrich
(St. Louis, MO).
(E)-2-(Acetoxymethyl)-6-[4-(3,5-dimethoxystyryl)phenoxy]tetrahydro-
2H-pyran-3,4,5-triyl Triacetate (18). Glucosylation of 15 (Scheme 1)
was performed according to procedures reported by Orsini et al. (18).
To a solution of 15 (256 mg, 1 mmol) in 1.25 M sodium hydroxide
(NaOH) (5 mL) was added a solution of glucosyl bromide (411 mg, 1
mmol) and benzyltrietylammonium bromide (108 mg, 0.39 mmol) in
chloroform. The reaction was vigorously stirred at 60 °C for 5 h. An
additional amount of glucosyl bromide (200 mg) was added, and the
reaction was heated for an extra 5 h. Ethyl acetate was added, and the
reaction was washed with water. The organic phase was dried using
MgSO4, and the solvent was evaporated under reduced pressure. 1H
NMR (CDCl3, 400 MHz): δ 2.02-2.07 (m, 12H), 3.8 (s, 6H), 4.15 (d,
1,3-Dimethoxy-5-[4-(trifluoromethyl)styryl]benzene (28a,b). Reaction
of (3,5-dimethoxybenzyl)triphenylphosphonium 20 (300 mg, 0.6 mmol)
and 4-(trifluoromethyl)benzaldehyde 24 (84 µL, 0.6 mmol) afforded
1
28a,b. Compound 28a, 4.7 mg. H NMR (CDCl3, 400 MHz): δ 3.84
(s, 6H), 6.43 (t, 1H, J ) 2 Hz), 6.68 (d, 2H, J ) 2.4 Hz), 7.10 (d, 2H,
J ) 2.8 Hz), 7.59 (s, 4H). 13C NMR (CDCl3, 100 MHz): δ 55.6 (2C),
100.7, 105 (2C), 125.8 (3C), 126.8 (2C), 127.8. 131.3, 138.8 (2C),
140.8, 161.2 (2C). Positive ion ESI-HRMS: calcd for C17H16O2F3 [M
+ H]+, 309.1102; found, 309.1089. Compound 28b, 22 mg. 1H NMR