Phytotoxic activity of quinones and resorcinolic lipid derivatives

Article abstract of DOI:10.1021/jf100108c

On the basis of the reported phytotoxic activity of sorgoleone and resorcinolic lipids identified from the root extracts of Sorghum bicolor, 8 resorcinolic lipid derivatives and 10 quinones with various side chain sizes were synthesized. The phytotoxicity of the compounds was tested against a monocot and a dicot species. The quinones were phytotoxic, whereas the resorcinolic lipids were not. Of the quinones, 2-hydroxy-5-methoxy-3- pentylcyclohexa-2,5-diene-1,4-dione, having a five-carbon side chain, showed phytotoxic activity similar to that of natural compound sorgoleone. This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society.

Full text of DOI:10.1021/jf100108c

J. Agric. Food Chem. 2010, 58, 4353–4355 4353
DOI:10.1021/jf100108c
Phytotoxic Activity of Quinones and Resorcinolic
Lipid Derivatives
C
ASSIA S. MIZUNO, AGNES M. RIMANDO,* AND STEPHEN O. DUKE
Natural Products Utilization Research Unit, Agricultural Research Service,
U.S. Department of Agriculture, P.O. Box 8048, University, Mississippi 38677-8048
On the basis of the reported phytotoxic activity of sorgoleone and resorcinolic lipids identified from
the root extracts of Sorghum bicolor, 8 resorcinolic lipid derivatives and 10 quinones with various
side chain sizes were synthesized. The phytotoxicity of the compounds was tested against a
monocot and a dicot species. The quinones were phytotoxic, whereas the resorcinolic lipids were
not. Of the quinones, 2-hydroxy-5-methoxy-3-pentylcyclohexa-2,5-diene-1,4-dione, having a five-
carbon side chain, showed phytotoxic activity similar to that of natural compound sorgoleone.
KEYWORDS: Sorgoleone; resorcinols; quinones; phytotoxic
INTRODUCTION
management, a group of resorcinolic lipids and quinones were
synthesized and tested for phytotoxicity against monocot and
dicot species.
Every year about 13% of the world’s crops are lost due to
damages caused by weed. The development of weed control
technology such as transgenic crops and synthetic herbicides
has made a great contribution to the improvement of crop yields
through the years. According to Bridges (1, 2) losses in agricul-
tural production would be 500% higher without the use of
herbicides. However, herbicide resistance and the sensitivity of
the public to the use of synthetic herbicides for food production
leave a place in the market for safer and more efficacious
herbicides.
Allelopathy is the inhibition of growth of a plant through the
production of phytotoxins released by another plant. This pheno-
menon represents warfare between neighboring plants competing
for light, water, and nutrients (3,4). There are several crop plants
in which allelopathic effects have been observed, including rice,
wheat, oats, sunflower, barley, and sorghum, with rice being the
most studied case.
MATERIALS AND METHODS
General Procedures for the Preparation of 26-35 (See also the
Supporting Information). Preparation of quinones was accomplished
according to the method of Poigny et al. (11). To a solution of com-
pounds 21-25 (1 mmol) in acetonitrile was added ammonium cerium(IV)
nitrate (2.5 mmol) dissolved in acetonitrile/water (7:3) at -7 °C. The
reaction was stirred for 2 h and then ether was added. The organic layer
was washed with water (3 ꢀ 10 mL), and the organic phases were
combined and dried over MgSO4. Removal of solvent under reduced
pressure gave a crude mixture that was purified over silica gel eluting with
hexanes/ethyl acetate.
2,5-Dimethoxy-3-pentylcyclohexa-2,5-diene-1,4-dione (27): 35% yield;
1H NMR (CDCl3, 400 MHz) δ 0.84 (t, 3H, J = 8 Hz), 1.27 (s, 4H), 1.34
(m, 2H), 2.38 (t, 2H, J = 8 Hz), 3.77 (s, 3H), 4.01 (s, 3H), 5.70 (s, 1H);
13C NMR (CDCl3, 100 MHz) δ 14.1, 22.6, 23.2, 28.5, 31.9, 56.6, 61.5,
105.5, 130.8, 156.0, 158.9, 182.6, 183.8. HRMS: calcd for C13H17O4
[M - H] 237.1126, found 237.1130.
Sorghum is considered to be one of the most important cereal
crops in the world (5). The allelopathic activity of this plant was
noticed due to the significant reduction of growth of other crops
when grown in rotation with sorghum (6).
3-Decyl-2,5-dimethoxycyclohexa-2,5-diene-1,4-dione (28): 32% yield;
1H NMR (CDCl3, 400 MHz) δ 0.86 (t, 3H, J = 8 Hz), 1.23 (s, 14H), 1.37
(s, 2H), 2.41 (t, 2H, J = 8 Hz), 3.79 (s, 3H), 4.03 (s, 3H), 5.71 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ 14.3, 22.8, 23.2, 28.8, 29.5 (2C), 29.7, 29.8
(2C), 32.0, 56.5, 61.5, 105.5, 130.9, 156.0, 158.9, 182.6, 183.7. HRMS: calcd
for C18H29O4 [M þ H] 309.2065, found 309.2086.
Sorgoleone (1, Figure 1) is a natural quinone released from
sorghum root exudates. The ability of sorghum crops to inhibit
the growth of weeds is attributed to sorgoleone. For this reason,
Sorghum species are used sometimes as cover crops in the south-
ern parts of the United States (7). The allelopathic activity of
sorgoleone has been reported in a number of studies (see, e.g.,
refs 8 and 9). Previous studies have also identified the resorci-
nolic lipid 4,6-dimethoxy-2-((8Z,11Z)-pentadeca-80,110,140-trienyl)-
benzene-1,3-diol (2, Figure 1) to be more phytotoxic than sorgo-
leone against lettuce germination (10). In our continuing search
for natural product and natural product-based herbicides for pest
2-Hydroxy-5-methoxy-3-pentylcyclohexa-2,5-diene-1,4-dione (32): 6.4%
yield; 1H NMR (CDCl3, 400 MHz) δ 0.84 (t, 3H, J = 8 Hz), 1.27 (s, 4H),
1.42 (t, 2H, J = 8 Hz), 2.40 (t, 2H, J = 8 Hz), 3.83 (s, 3H), 5.81 (s, 1H), 7.33
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.2, 22.6, 22.7, 27.9, 31.8, 56.9,
102.4, 119.4, 151.8, 161.3, 181.9, 183.0. HRMS: calcd for C12H15O4
[M - H] 223.0970, found 223.0966.
2-Hydroxy-5-methoxy-3-tetradecylcyclohexa-2,5-diene-1,4-dione (35):
27% yield; 1H NMR (CDCl3, 400 MHz) δ 0.86 (t, 3H, J = 8 Hz), 1.23
(s, 22H), 1.43 (m, 2H), 2.42 (t, 2H, J = 8 Hz), 3.84 (s, 3H), 5.82 (s, 1H),
7.27 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.3, 22.8, 22.9, 28.2, 29.5,
29.6, 29.7, 29.8 (6C), 32.1, 56.9, 102.3, 119.4, 151.7, 161.3, 181.9, 183.0.
HRMS: calcd for C21H33O4 [M - H] 349.2378, found 349.2356.
*Corresponding author [telephone (662) 915-1037; fax (662) 915-1035;
e-mail agnes.rimando@ars.usda.gov].
This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society
Published on Web 03/16/2010
pubs.acs.org/JAFC

4354 J. Agric. Food Chem., Vol. 58, No. 7, 2010
Mizuno et al.
Figure 1. Chemical structures of sorgoleone (1) and resorcinolic lipid derivative (2).
Table 1. Effects of Resorcinols and Quinones on Development of Lettuce
and Agrostis Seedlingsa
Scheme 1a
compound
concentration (mM)
lettuceb,c
agrostisb
27
0.01
0.03
0.1
0.3
1
0
0
0
1
2
0
0
1
3
4
28
0.01
0.03
0.1
0.3
1
0
0
0
0
2
0
0
0
0
1
32
0.01
0.03
0.1
0.3
1
0
0
0
3
5
0
0
2
3
4
a Reagents and conditions: (a) BuLi, THF, 12 h, room temperature; (b) Pd/C,
MeOH, 12 h, room temperature; (c) BBr3, DCM, -40 °C f room temperature, 12 h.
35
0.01
0.03
0.1
0.3
1
0
0
0
1
1
0
0
0
0
0
any growth inhibitory effect. The resorcinols and quinones
synthesized in this work lack the triene unit in the side chain that
the natural phytotoxic compound 1 has. Lack of activity of the
resorcinols could not be due to the lack of the triene unit. Previous
work has revealed that the unsaturation is not essential for
biological activity (13, 14). Additionally, the quinones that were
found to be active in the present study did not have the triene unit.
Of the quinones with side chains varying from 1 to 14 carbons
(Scheme 4), compound 32 with a side chain of 5 carbons showed
the best activity. At 0.1 mM concentration, 32 had moderate
toxicity against bentgrass growth and development, and at 1.0 mM
it completely inhibited the germination of lettuce (Table 1). This
activity is very similar to that of sorgoleone as reported ear-
lier (15). Compound 27, a dimethoxylated analogue of 32, was the
second best compound, with growth inhibitory activity starting at
0.1 mM against bentgrass. At 1 mM, the development of seedlings
was strongly inhibited. However, 27 showed weaker phytotoxi-
city against lettuce compared to 32, even in higher concentrations.
These results suggest that the hydroxyl group is preferred at the
C2 position of the quinone ring for phytotoxic activity against
lettuce.
Quinone 28, which has a 10-carbon side chain, showed weak
growth inhibitory activity at the highest concentration (1.0 mM)
against lettuce and bentgrass. Compound 34, the natural com-
pound 5-O-methylembelin, is known to be toxic to fish (16).
However, this compound lacked phytotoxic activity.
Previous work done by Barbosa et al. (13) revealed that
saturation of the triene in the side chain of sorgoleone resulted
in a compound with phytoxicity very similar to that of the natural
compound. However compound 35, having a 14-carbon side
chain, just 1 carbon less than Barbosa’s compound, had no
phytotoxic activity in our studies.
sorgoleone
0.01
0.03
0.1
0.3
1
0
0
1
3
4
0
0
0
0
0
a The other compounds tested (4-6, 10-14, 26, 29-31, 33, and 34) did not
show phytotoxic activity at any of the concentrations tested. b Ratings are based on
visual inspection of growth on a scale of 0 (no activity, not phytotoxic) through 5
(highly phytotoxic, complete inhibition of seedling growth). c Data on phytotoxicity of
sorgelone against lettuce are from Rimando et al. (15).
Bioassay. Lettuce seeds (Lactuca sativa L. cv. Iceberg A) were
obtained from Burpee Seed Co. and creeping bentgrass seeds (Agrostis
stolonifera var. Penncross) from Turf-Seed (Hubbard, OR). These species
were selected because we have used them to evaluate thousands of
synthetic and natural compounds for phytotoxicity with the method of
Dayan et al. (12). Compounds were subjected to phytotoxicity assays at
concentrations ranging from 0.01 to 1 mM.
RESULTS AND DISCUSSION
The activities of several resorcinols and quinones against
lettuce and bentgrass growth and development are shown in
Table 1.
Resorcinols 4-6 (Scheme 1) and 10-14 (Schemes 2 and 3) did
not show any phytotoxic activity. Thus, the size of the side chain
did not have any effect on toxicity. Compounds 10, 12, and 14,
with a side chain of11 carbons, and compounds 6, 11, and 13, with
a side chain of 15 carbons, lacked activity. To study the effects
that different substituents have on phytotoxicity, several alkoxy
groups were introduced around the benzene ring such as acetoxy
(11 and 12), methoxy (4), hydroxy (6 and 10), and ethoxy (13 and
14). Although these groups generated diversity, they did not have
In conclusion, synthesis of resorcinols and quinones was
accomplished using simple and economic synthetic procedures.
The phytotoxic activity of these compounds was investigated
against a monocot and a dicot species. In the present work, the

Article
J. Agric. Food Chem., Vol. 58, No. 7, 2010 4355
Scheme 2a
a Reagents and conditions: (a) BuLi, THF, -78 °Cf room temperature, 12 h; (b), Pd/C, MeOH, 12 h, room temperature; (c) TBAF, THF, 45 min, room temperature.
Scheme 3 a
Scheme 4 a
a Reagents and conditions: (a) acetyl chloride, TEA, DCM, 0 °Cf room
temperature, 12 h; (b) EtI, K2CO3, DMF, room temperature, 12 h.
quinones showed better activity compared to the resorcinols.
Compound 32, the most active quinone found in this set of
compounds, showed activity similar to that of the natural
compound sorgoleone with the advantage of being much easier
to synthesize than the natural compound.
a Reagents and conditions: (a) nBuLi, HMPA, THF, -40 °Cf room tempera-
ture, 12 h; (b) CAN, CH3CN, 1 h, -7 °C f room temperature.
(8) Putnam, A. R.; Defranck, J.; Barnes, J. P. Exploitation of allelo-
pathy for weed control in annual and perennial cropping systems.
J. Chem. Ecol. 1983, 8, 1001–1010.
ACKNOWLEDGMENT
(9) Forney, D. R.; Foy, C. L.; Wolf, D. D. Weed suppression in no-till
alfalfa (Medicago sativa) by prior cropping with summer-annual
forage grasses. Weed Sci. 1985, 33, 490–497.
(10) Rimando, A. M.; Dayan, F. E.; Streibig, J. C. PSII inhibitory activity
of resorcinolic lipids from Sorghum bicolor. J. Nat. Prod. 2003, 66,
42–45.
We thank Robert Johnson for technical support.
Supporting Information Available: Experimental details and
analytical data for compounds 4-6, 10-14, 26, 29-31, 33, and
34. This material is available free of charge via the Internet at
http://pubs.acs.org.
(11) Poigny, S.; Guyot, M.; Samadi, M. Total synthesis of maesanin and
analogs. Tetrahedron 1998, 54, 14791–14802.
LITERATURE CITED
(12) Dayan, F. E.; Hernandez, A.; Allen, S. N.; Moraes, R. M.; Vroman,
J. A.; Avery, M. A.; Duke, S. O. Comparative phytotoxicity of
artemisinin and several sesquiterpene analogs. Phytochemistry 1999,
50, 607–614.
(13) Barbosa, L. C. de A.; Ferreira, M. L.; Demuner, A. J. Preparation
and phytotoxicity of sorgoleone analogues. Quim. Nova 2001, 24,
751-755.
(14) Lima, L. S.; Barbosa, L. C. de A.; de Alvarenga, E. S.; Demuner, A.
J.; da Silva, A. A. Synthesis and phytotoxicity evaluation of
substituted para-benzoquinones. Aust. J. Chem. 2003, 56, 625–630.
(15) Rimando, A. M.; Dayan, F. E.; Czarnota, M. A.; Weston, L. A.;
Duke, S. O. A new photosystem II electron transfer inhibitor from
Sorghum bicolor. J. Nat. Prod. 1998, 61, 927–930.
(1) Bridges, D. C. Crop Losses Due to Weeds in the United States;
Bridges, D. C., Ed.; Weed Science Society of America: Champaign, IL,
1992; 403 pp.
(2) Bridges, D. C. Impact of weeds on human endeavours. Weed
Technol. 1994, 8, 392–395.
(3) Inderjit; Duke, S. O. Ecophysiological aspects of allelopathy. Planta
2003, 217, 529–539.
(4) Bais, H. Pal.; Park, S. W.; Weir, T. L.; Callaway, R. M.; Vivanco,
J. M. How plants communicate using the underground information
superhighway. Trends Plant Sci. 2004, 9, 26–32.
(5) Doggett, H. Sorghum; Longman Scientific and Technical, co-published
in the United States with Wiley: New York, 1988; 516 pp.
(6) Breazeale, J. F. The injurious after-effects of sorghum. J. Am. Soc.
Agron. 1924, 16, 689–700.
(16) Miles, D. H.; Payne, M. Synthesis of 5-O-methylembelin. Tetra-
hedron 2001, 57, 5769–5772.
(7) Einhellig, F. A.; Rasmussen, J. A. Prior cropping with grain sorghum
inhibits weeds. J. Chem. Ecol. 1989, 15, 951–960.
Received for review September 21, 2009. Accepted March 2, 2010.