Herbicidal activity of cineole derivatives

Article abstract of DOI:10.1021/jf101827v

Essential oils and their constituents have potential as ecologically acceptable pesticides that may also have novel modes of action. In this work hydroxy and ester derivatives of the naturally occurring monoterpenoids 1,8-cineole 3, the main component in

Full text of DOI:10.1021/jf101827v

J. Agric. Food Chem. 2010, 58, 10147–10155 10147
DOI:10.1021/jf101827v
Herbicidal Activity of Cineole Derivatives
‡
,
,†
A
LLAN F. M. BARTON,† BERNARD
DELL
AND
ALLAN R. KNIGHT*
†School of Chemical and Mathematical Sciences and ‡Sustainable Ecosystems Research Institute,
Murdoch University, South Street, Murdoch, Western Australia, 6150
Essential oils and their constituents have potential as ecologically acceptable pesticides that may also
have novel modes of action. In this work hydroxy and ester derivatives of the naturally occurring
monoterpenoids 1,8-cineole 3, the main component in most eucalyptus oils, and 1,4-cineole 4 were
prepared and their pre-emergence herbicidal activity against annual ryegrass (Lolium rigidum) and
radish (Raphanus sativus var. Long Scarlet) investigated in laboratory-based bioassays. 1,8-Cineole,
eucalyptus oil and all derivatives showed a dose-dependent herbicidal activity against annual ryegrass
and radish with many of the derivatives showing improved herbicidal activity relative to 1,8-cineole and
high-cineole eucalyptus oil. Increased activity of cineole ester derivatives compared to their associated
hydroxy-cineole and carboxylic acid was not observed. No relationship between lipophilicity of the
carboxylic acid portion of cineole ester derivatives and herbicidal activity was observed. The results
indicate that these cineole derivatives could be environmentally acceptable herbicides.
KEYWORDS: Cineole; eucalyptus oil; herbicidal; pre-emergence; germination; ryegrass; radish;
bioactivity; phytotoxicity
INTRODUCTION
seedling development and establishment. A major component in
the essential oils of Salvia species is 1,8-cineole, which has been
shown by Halligan (11) to be one of the most potent allelochemicals
released by Artemisia species and also by Kumar and Motto (12)
in Eucalyptus species. However, Angelini et al. (13) found no
significant germination inhibition by 1,8-cineole of a number
of crop and weed species, and some field tests indicated that
1,8-cineole has low herbicidal activity (11, 14).
A major impact of weeds in agricultural systems is reduced
crop yield as a result of strong competition for space, nutrients
and sunlight (1, 2). Thus weed management is an important
aspect of agricultural practice. Chemical control has been a signifi-
cant part of management strategies since the 1940s when synthetic
chemicals were introduced for this purpose, but in recent decades
public concerns over the use of synthetic chemicals and the
development of resistance of weeds to synthetic chemicals have
led to increased investigation of the herbicidal activity of plant-
derived secondary metabolites (3). Such natural products not
only may be more environmentally acceptable than synthetic
pesticides but also may have novel mechanisms of action com-
pared to the current suite of herbicides to which weeds are
developing resistance (4).
It is not surprising that there are natural products with phyotoxi-
city. Many organisms have evolved compounds to inhibit growth,
or facilitate attack and digestion of plants that are potential
competitors. The triketone, bialaphos and glufosinate herbicides,
derived from natural products, have novel phytotoxic mechan-
isms not previously seen in synthetic herbicides (5). The bleaching
triketone herbicide mesotrione 1 was developed from the allelo-
chemical leptospermone 2 found in the roots of the bottle brush
Callistemon citrinus (6).
1,4-Cineole (1-isopropyl-4-methyl-7-oxa-bicyclo[2.2.1]heptane) 4,
a less abundant naturally occurring structural isomer of 1,8-cineole,
also inhibits seed germination and plant growth (9, 15, 16). Vaughn
and Spencer (9) showed that 1,4-cineole completely inhibited the
germination of wheat, large crabgrass, redroot pigweed and ryegrass
while 1,8-cineole completely inhibited the germination of corn, wheat,
alfalfa, large crabgrass, redroot pigweed and annual ryegrass.
Romagni et al. (16,17) also examined the effects of 1,4-cineole,
cinmethylin 5 and 1,8-cineole on lettuce seedlings. Cinmethylin,
the o-methylbenzyl ether of racemic 2-exo-hydroxy-1,4-cineole 6,
has been used as a pre-emergence herbicide. The concentration at
which there was 50% inhibition in root growth was an order of
magnitude lower for the natural monoterpene 4 than for its
derivative cinmethylin. Romagni and co-workers also found that
the lowest concentration needed to give maximum phytotoxic
effect was an order of magnitude higher for cinmethylin than for
1,4-cineole. Their original results suggested that on uptake by a
plant cinmethylin was metabolically cleaved to give a hydroxy-
lated cineole and a benzyl ether portion. The herbicidal activity of
cinmethylin is postulated to be due primarily to the hydroxylated
cineole portion with the benzyl portion having little role in any
bioactivity. The benzyl ether derivative 5 is manufactured to give
a compound with increased molecular weight and reduced vol-
atility compared to 1,4-cineole. If 1,4-cineole were applied in the field,
A wide range of classes of volatile monoterpenes, including
oxygenated monoterpenes such as 1,8-cineole (1,3,3-trimethyl-2-
oxabicyclo[2.2.2]octane) 3, inhibit plant growth (7-9). Muller
et al. (10) demonstrated in field studies that volatile monterpenes
released by Salvia leucophylla gave greatest inhibition during
*Author to whom correspondence should be addressed. Tel: 61 08
9360 6871. Fax: 61 08 9360 6452. E-mail a.knight@murdoch.edu.au.
© 2010 American Chemical Society
Published on Web 08/17/2010
pubs.acs.org/JAFC

10148 J. Agric. Food Chem., Vol. 58, No. 18, 2010
Barton et al.
it would evaporate before a sufficient amount was taken in by
target plants.
While allelopathic and herbicidal activity of 1,8-cineole against
some plant species has been established, there is clearly a range of
activities, and there are no reports of either derivatization of 1,8-
cineole for the purposes of reducing its volatility or subsequent
testing of the herbicidal activity of derivatives. Low herbicidal
activity found in some field tests may be due to the high volatility
of 1,8-cineole causing reduced uptake by plants. 1,8-Cineole and
other phytochemicals offer the potential to produce new herbi-
cides with novel modes of action, and while modification of their
structures may be needed to improve efficacy, their environmen-
tal impact is likely to be less than that of synthetic herbicides.
One aim of this work was to prepare derivatives of 1,8-cineole
with reduced volatility but equivalent or increased phytotoxicity.
The study investigated whether ester derivatives of 1,8-cineole
and 1,4-cineole would have higher phytotoxicity than their
corresponding hydroxylated cineoles and carboxylic acids, and
whether phytotoxicity would increase as the nonpolar carboxylic
acid portion of the esters increased in size and hence lipophilicity.
Pre-emergence herbicidal activity of the cineole derivatives and
the corresponding carboxylic acids was assessed, and the cineole
isomers were compared.
MATERIALS AND METHODS
Instruments and Chemicals. Unless otherwise stated, 1H and 13C
NMR spectra were measured at 300 and 75 MHz respectively, on a Bruker
Avance DPX-300 spectrometer, for solutions in deuterochloroform
(CDCl3) with internal standard tetramethylsilane (TMS) (1H, 13C,
δ 0.00) and residual chloroform (1H, δ 7.26; 13C, δ 77.0). The signals in
the 13C spectra were assigned with the aid of DEPT experiments, and
assignment of signals with the same superscripts are interchangeable. All
coupling constants are given in hertz. Infrared spectra were recorded on a
Nicolet 850 series III FTIR, as thin films between KBr disks for oils, and
using a diffuse reflectance unit for solids. High resolution mass spectra
were obtained on a V.G. Autospec high resolution mass spectrometer at
the University of Western Australia, Perth, Australia. All chemicals and
reagents were purchased from standard commercial suppliers.
Synthesis of 1,8-Cineole Derivatives. 3-Hydroxy-1,8-cineole ((()-
exo-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-ol) 7 was synthesized in an
adaptation of the method of de Boggiatto et al. (18) (Figure 1). The ester
derivatives 8a-e were prepared using well established reaction methods.
The acetate 8a was prepared by reaction of 7 with acetic anhydride and dry
pyridine, and esters 8b-e were prepared by reaction of 7 with the
appropriate acid chloride.
2-endo-Hydroxy-1,8-cineole ((1R,6R)-1,3,3-trimethyl-2-oxabicyclo-
[2.2.2]octan-6-ol) 9 was obtained as the primary metabolite of a novel
bacterium grown on 1,8-cineole as sole carbon source. The bacteria were
isolated by inoculating liquid growth medium containing 1,8-cineole as
carbon source with aliquots of deionized water in which eucalyptus leaves
had been stirred.
Synthesis of 1,4-Cineole Derivatives. Synthesis of the 1,4-cineole
esters is outlined in Figure 2. 2-exo-Hydroxy-1,4-cineole ((()-exo-4-
isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol) 10 was prepared as
described by Payne (19) and then converted to esters 11a-e in the same
manner as for the 1,8-cineole esters. Cinmethylin 5 was prepared from
alcohol 10 as described by Silvestre et al. (20).
Figure 1. Synthesis of 1,8-cineole esters 8a-e. Reagentsand conditions:
(a) (18) CrO3, CH3COOH/(CH3CO)2O, 4 °C, 48 h, rt, 10 h; (b) (18) NaBH4,
dry EtOH, rt, 2 h, reflux, 5 h; (c) dry pyridine, (CH3CO)2O, dry CH2Cl2,
reflux, 22 h; (d) dry pyridine, RCOCl, dry CH2Cl2, reflux, 5 h.
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-yl butanoate 8b was
recovered in 47% yield as a very pale yellow oil. (Found: (M þ 1)þ,
241.1791, C14H25O3 requires (M þ 1), 241.1804.) IR (cm-1) 2968, 2932
(C-H, str), 1734 (OCO ester).
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-yl hexanoate 8cwas
obtained as a clear oil in a yield of 63%. (Found: (M - H)þ, 267.1947,
C16H27O3 requires (M - H), 267.1960.) IR (cm-1) 2964, 2931, 2869
(C-H str), 1734 (OCO ester).
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-yl 3,3-dimethyl-
butanoate 8d was recovered as white needles after recrystallization
from ethyl acetate in a yield of 95% (mp 54-55 °C). (Found: (M þ 1)þ,
269.2117, C16H29O3 requires (M þ 1), 269.2117.) IR (cm-1) 2961, 2934,
2866 (C-H, str), 1725 (OCO ester).
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-yl benzoate 8e was
recovered as white crystals in a yield of 68% (mp 75-77 °C). (Found: (M þ 1)þ,
275.1662, C17H23O3 requires (M þ 1), 275.1647.) IR (cm-1) 3065, 3012
(Ar-H), 2992, 2964, 2924 (C-H str), 1713 (OCO ester) 1601, 1582 (aromatic).
(()-exo-4-Isopropyl-1-methyl-2-(2-methylbenzyloxy)-7-oxabicyclo-
[2.2.1]heptane 5 was recovered as a pale yellow oil in a yield of 59%.
(()-exo-4-Isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptan-2-ol 10 was
recovered as white crystals in a yield of 68% after recrytallisation from
hexane (mp 83-86 °C).
(()-exo-4-Isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl ethanoate
11a was recovered as a pale yellow oil in a yield of 58%. (Found: Mþ,
212.1412, C12H20O3 requires M, 212.1412.) IR (cm-1) 2964, 2877 (C-H,
str), 1740 (OCO, ester).
(()-exo-4-Isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl butanoate
11b was recovered as a pale yellow oil in a yield of 74%. (Found: Mþ,
240.1729, C14H24O3 requires M, 240.1725.) IR (cm-1) 2964, 2877 (C-H,
str), 1734 (OCO ester).
(()-exo-4-Isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl hexanoate
11c was recovered as a nearly colorless oil in a yield of 75%. (Found: Mþ,
268.2044, C16H28O3 requires M, 268.2038.) IR (cm-1) 2959, 2873 (C-H,
str), 1734 (OCO ester).
Proton NMR, carbon-13 NMR and mass spectral data for compounds
are provided in Tables 1, 2, 3, 4 and 5.
(()-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-one 6 was recovered in a
yield of approximately 30%, and its 1H NMR spectrum was consistent
with published spectra (18, 21).
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-ol 7 was recovered
in a yield of approximately 98%, and its 1H NMR spectrum was consistent
with published spectra (18, 21).
Esters 8a-e were recovered in yields ranging from 47 to 95%.
(()-exo-1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octan-5-yl ethanoate 8a was
recovered in 95% yield as a colorless oil.

Article
J. Agric. Food Chem., Vol. 58, No. 18, 2010 10149
Figure 2. Synthesisofcinmethylin, 5, and1,4-cineole esters11a-e. Reagents and conditions:(a) (19) t-butyl hydroperoxide, CH2Cl2, VO(AcAc)2, reflux, 2 h;
(b) (19) p-TSA, reflux, 1.5 h; (c) (20) CH3C6H4CH2Cl, NaH, dry THF, N2, reflux, 15 h; (d) dry pyridine, (CH3CO)2O, dry CH2Cl2, reflux, 20 h; (e) dry pyridine,
RCOCl, dry CH2Cl2, reflux, 5 h.
Table 1. Proton NMR Data for 1,8-Cineole Derivatives
proton
6
7
8a
1.69-1.78, m
8b
1.59-1.77, m
2-H2
2.12-2.24, m
1.98-2.09, m
2.06, dd, J = 10.3, 13.8
4.15, ddd, J = 2.0, 6.2, 10.3
1.69, ddd, J = 3.2, 6.1, 13.8
1.33-1.42, m
1.52-1.62, m
1.33-1.42, m
2.10, dd, J = 10.6, 14.1
4.98, ddd, J = 2.2, 6.0, 10.6
1.69-1.78, m
1.37-1.53, m
2.02-2.13, m
1.37-1.53, m
1.54-1.68, m
1.12, s
2.11, dd, J = 10.6, 14.1
5.00, ddd, J = 2.2, 6.0, 10.5
1.59-1.77, m
1.40-1.53, m
2.02-2.10, m
3-H
4-H
5-H2
2.38, dd, J = 2.9, 18.9
1.54-1.70, m
1.72-1.86, m
1.72-1.86, m
2.12-2.24, m
1.11, s
6-H2
1.40-1.53, m
1.52-1.62, m
1.11, s
1.59-1.77, m
1.11, s
1.24, s
7-H3
9-H3
1.20, s
1.27, s
1.24, s
1.44, s
2.14 (br s, 1H, OH)
1.24, s
1.35, s
2.05 (s, 3H, COCH3)
10-H3
other
1.35, s
0.96 (t, 3H, J = 7.4, 40-H3),
1.66 (sept, 2H, J = 7.4, 30-H2),
2.28 (t, 2H, J = 7.5, 20-H2)
proton
2-H2
3-H
8c
8d
8e
9a
1.54-1.76, m
2.11, dd, J = 10.6, 14.1
4.99, ddd, J = 2.2, 6.0, 10.5
1.55-1.76, m
2.13, dd, J = 10.6, 14.1
5.00, ddd, J = 2.1, 6.1, 10.5
1.85-1.95, m
2.25, dd, J = 10.5, 14.2
5.26, ddd, J = 2.1, 6.1, 10.5
3.68-3.78, m
1.26-1.37, m
2.45-2.58, m
1.46-1.61, m
1.84-2.03, m
2.04-2.08, m
1.46-1.61, m
1.84-2.03, m
1.10, s
4-H
5-H2
1.54-1.76, m
1.41-1.53, m
2.01-2.13, m
1.41-1.53, m
1.54-1.76, m
1.11, s
1.24, s
1.55-1.76, m
1.38-1.54, m
2.02-2.15, m
1.38-1.54, m
1.55-1.76, m
1.11, s
1.85-1.95, m
1.59-1.72, m
2.08-2.19, m
1.43-1.57, m
1.59-1.72, m
1.16, s
1.28, s
6-H2
7-H3
9-H3
1.24, s
1.36, s
1.20, s
1.28, s
10-H3
other
1.35, s
1.48, s
0.90 (t, 3H, J = 6.9, 60-H3), 1.28-1.38
(m, 4H, 40-H2, 50-H2), 1.54-1.76
(m, 30-H2), 2.29 (t, 2H, J = 7.7, 20-H2),
1.04 (s, 9H, C(CH3)3),
2.19 (s, 2H, 20-H2)
7.45 (t, 2H, J = 7.7, 30-H, 50-H),
7.54-7.66 (m, 1H, 40-H),
8.05 (d, 2H, J = 7.8, 20-H,60-H)
1.46-1.61 (m, OH)
a Compound 9 has 1 H atom on C2 and 2 H atoms on C3 while 7 and 8a-e have 2 H atoms on C2 and 1 H atom on C3.
(()-exo-4-Isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl 3,3-dimethyl-
butanoate 11d was recovered in a yield of 59% as a pale yellow oil. (Found:
Mþ, 268.2039, C16H28O3 requires M, 268.2038.) IR (cm-1) 2960, 2874
(C-H str), 1732 (OCO ester).
(()-exo-4-Isopropyl-1-methyl-7-oxabicyclo[2.2.1]heptan-2-yl benzoate
11e was obtained in a yield of 92% as white crystals after recrystallization
from ethanol (mp 77-79 °C). (Found: (M þ 1)þ, 275.1643, C17H23O3
requires (M þ 1), 275.1647.) IR (cm-1) 3067 (Ar-H), 2968, 2942, 2874
(C-H, str), 1712 (OCO ester), 1600, 1581 (aromatic).
November 2002, and radish seeds (Raphanus sativus var. Long Scarlet)
were a commercially available variety (Mr Fothergill’s Seeds Pty Ltd.).
Seed Treatment. Seeds were surface sterilized in 2% sodium hypo-
chlorite solution for 10 min, rinsed 3 times with sterile deionized water and
then imbibed for approximately 15 h in sterile deionized water.
Pre-emergence Bioassays. Water agar was prepared by autoclaving
(103.4 kPa, 121 °C, 30 min) 4.0 g of agar (BBL Agar, grade A) in 500 mL
of deionized water containing calcium and boron at concentrations of
0.05 mol L-1 and 0.001 mol L-1, respectively. Under sterile conditions, the
agar was poured into 55 mm plastic Petri dishes (or sterile Pyrex dishes for
chloroform solutions) to a depth of approximately 2 mm and allowed to
Seed Sources. Annual ryegrass seeds (Lolium rigidum) were obtained
from the Wongan Hills Research Station 2EA, Western Australia, in

10150 J. Agric. Food Chem., Vol. 58, No. 18, 2010
Table 2. Proton NMR Data for 1,4-Cineole Derivatives
Barton et al.
proton
5
10
3.70-3.81, m
1.34-1.61, m
2.10-2.15, m
1.34-1.61, m
1.34-1.61, m
1.42, s
11a
11b
2-H
3-H2
3.54, dd, J = 2.4, 6.7, 12.1
1.40-1.64, m
1.95, dd, J = 6.7, 12.1
4.88, dd, J = 2.6, 7.3
1.45-1.64, m
2.07-2.21, m
1.45-1.64, m
1.45-1.64, m
1.39, s
4.88, dd, J = 2.6, 7.2
1.43-1.73, m
2.02-2.21, m
1.43-1.73, m
1.43-1.73, m
1.38, s
5-H2
6-H2
7-H3
8-H
1.40-1.64, m
1.40-1.64, m
1.47, s
2.11, sept, J = 6.9
0.99, d, J = 6.9
0.97, d, J = 6.9
2.10-2.15, m
0.96, d, J = 6.9
0.97, d, J = 6.9
1.89 (br d, 1H, J = 8.8, OH)
2.07-2.21, m
0.97, d, J = 6.9
0.98, d, J = 6.8
2.07 (s, 3H, 20-H)
2.02-2.21, m
0.96, d, J = 6.8
0.98, d, J = 6.8
9-H3
10-H3
other
2.32 (s, 3H, Ar CH3), 4.36 þ 4.54 (AB system, 2H,
J = 12.4, 10-H), 7.11-7.20 (m, 3H, Ar4-H,
Ar5-H, Ar6-H), 7.30-7.35 (m, 1H, Ar3-H)
0.95 (t, 3H, J = 7.4, 40-H), 1.43-1.73
(m, 2H, 30-H2), 2.31
(t, 2H, J = 7.3, 20-H)
proton
11c
11d
11e
2-H
3-H2
4.87, dd, J = 2.6, 7.2
1.55-1.66, m
2.16, dd, J = 7.2, 13.2
4.83, dd, J = 2.6, 7.2
1.44-1.53, m
2.17, dd, J = 7.2, 13.2
5.10, dd, J = 2.4, 7.2
1.54-1.71, m
2.27, dd, J = 7.2, 13.0
5-H2
6-H2
1.42-1.53, m
1.55-1.66, m
1.42-1.53, m
1.55-1.65, m
1.54-1.71, m
1.55-1.65, m
1.54-1.71, m
1.55-1.66, m
1.38, s
7-H3
8-H
1.40, s
1.93-2.14, m
0.96, d, J = 6.9
1.48, s
2.15, sept, J = 6.9
1.00, d, J = 6.9
2.10, sept, J = 6.9
0.96, d, J = 6.9
9-H3
10-H3
other
0.97, d, J = 6.9
0.97, d, J = 6.9
1.03, s, C(CH3)3), 2.22 (s, 2H, 20-H)
1.00, d, J = 6.9
0.89 (t, 3H, J = 6.9, 60-H), 1.26-1.35
(m, 4H, 40-H2, 50-H2), 1.55-1.66
(m, 2H, 30-H2), 2.32 (t, 2H, J = 7.7, 20-H)
7.43 (t, 2H, J = 7.6, 30,50-H),
7.56 (t, 1H, J = 7.2, 40-H),
8.03-8.12 (m, 2H, 10,60-H)
Table 3. Carbon-13 NMR Data for 1,8-Cineole Derivatives
carbon
8b
8c
8d
8e
C1
C2
70.00
40.42
72.53
37.55
21.09
30.15
26.77
73.14
30.17
30.52
173.28
69.99
40.40
72.53
37.52
21.07
30.13
26.75
73.12
30.15
30.51
173.46
70.04
40.57
70.08
40.46
C3
C4
72.29
37.72
73.33
37.71
C5
C6
21.17
30.17
21.16
30.16
C7
C8
26.77
73.18
26.77
73.10
C9
30.57
30.57
30.11
30.88
C10
CdO
other
172.01
29.72 (C(CH3)3), 30.87
(C-30), 48.37 (C-20)
166.17
128.41 (C-30, 50), 129.53 (C-20, 60),
130.42 (C-10), 132.94 (C-40)
13.71 (C-40), 18.39
(C-30), 36.72 (C-20)
13.87 (C-60), 22.29 (C-50),
24.56 (C-40), 31.30 (C-30),
34.76 (C-20)
solidify. A solution (1 mL) of the test compound in the required organic
solvent (Table 6) was introduced into the Petri dishes using a micropipet,
and the dishes were left open in a laminar flow cabinet for 3 h to allow
evaporation of the organic solvent. Pre-emergence bioassays were carried
the 1,8-cineole solutions. The deionized water/Tween 80 solution, contain-
ing calcium and boron as above, was autoclaved prior to preparation of
the 1,8-cineole and eucalyptus oil solutions. All glassware used in the
preparation of these solutions was washed with 2% sodium hypochlorite
solution and then rinsed with sterile deionized water.
out at solution concentrations of 1, 0.1, 0.01, 1 ꢀ 10-3 and 1 ꢀ 10-4 mol L-1
.
Filter paper bioassays were used for 1,8-cineole and eucalyptus oil.
Filter papers (Whatman number 4) were autoclaved, oven-dried and
placed into autoclaved pyrex Petri dishes (55 mm) under sterile conditions.
1,8-Cineole solution or eucalyptus oil solution (1 mL) was transferred onto
the filter paper using a micropipet, the lid placed on the Petri dish and the
dish sealed with plastic food wrap. The 1,8-cineole and eucalyptus oil were
prepared in aqueous solution with 3.4 ꢀ 10-4 g mL-1 of the nonionic
surfactant Tween 80 (polyoxyethylene (20) sorbitan monooleate). Con-
centrations of 1,8-cineole solutions wereat the molar concentrations stated
For pre-emergence bioassays, ten seeds were placed in each Petri dish and
then sealed with plastic food wrap. At each concentration and for controls,
five replicates were used (i.e., 10 seeds in each of 5 Petri dishes). The Petri
dishes were placed randomly in a tray with Styrofoam supports to angle the
dishes at approximately 70° to the horizontal. Angling Petri dishes gave
straighter root and shoot growth than placing them flat. Petri dishes with
1,8-cineole and eucalyptus oil were placed flat. The tray was incubated under
light (135 to 195 μEm-2 s-1 photosynthetic active radiation) at 25 °C for 72 h.
Two controls, one with and one without solvent, were used for each experi-
ment. For solvent controls, solvent (1 mL) was pipetted onto the surface of the
agar and the Petri dish left open in a laminar flow cabinet for three hours. The
nonsolvent control consisted of the same agar solution in Petri dishes that
were similarly left open in a laminar flow cabinet for three hours.
above, and the high-cineole eucalyptus oil solutions were (in g mL-1
)
0.154, 1.54 ꢀ 10-2, 1.54 ꢀ 10-3, 1.54 ꢀ 10-4 and 1.54 ꢀ 10-5. These
concentrations were chosen to give a 1,8-cineole concentration in the
eucalyptus oil solutions that approximately matched its concentrations in

Article
J. Agric. Food Chem., Vol. 58, No. 18, 2010 10151
Table 4. Carbon-13 NMR Data for 1,4-Cineole Derivatives
carbon
11a
11b
11c
11d
11e
C1
C2
84.4
78.4
84.42
78.08
43.23
88.73
33.50
31.38
16.32
32.45
17.91a
18.12a
173.38
84.47
78.14
43.26
88.79
33.53
31.43
16.37
32.49
17.96a
18.17a
173.66
88.81
78.22
43.26
84.32
33.62
31.72
16.59
32.46
18.00a
18.13a
172.15
88.86
78.98
43.06
84.69
33.68
31.71
16.54
32.45
18.04a
18.13a
166.24
C3
C4
43.2
88.7
C5
C6
33.4
31.3
C7
C8
16.3
32.5
C9
17.9
18.1
C10
CdO
other
170.7
21.1 (C-20)
13.62 (C-40), 18.47 (C-30),
36.30 (C-20)
13.91 (C-60), 22.32 (C-50),
24.72 (C-40), 31.32 (C-30),
34.46 (C-20)
29.69 (C(CH3)3), 30.79 (C-30),
47.94 (C-20)
128.32 C-30, 50), 29.68 C-20, 60),
130.32 (C-10), 132.96 (C-40)
a Assignment of signals with the same superscript in the spectra is interchangeable.
Table 5. Mass Spectral Data for 1,8-Cineole and 1,4-Cineole Derivatives
compound
MS data m/z (rel int)
8b
8c
8d
8e
240 (Mþ, 17%), 239 (16), 226 (12), 225 (84), 223 (22), 153 (100), 152 (35), 151 (23), 147 (16), 137 (37), 135 (55), 11 (11)
269 (M þ 1, 100%), 268 (M, 11), 267 (18), 254 (13), 253 (78), 252 (10), 251 (31), 175 (36)
269 (M þ 1, 100%), 268 (M, 10), 254 (11), 253 (73), 251 (15), 175 (20), 153 (95), 152 (36), 151 (19), 137 (73), 135 (57)
275 (M þ 1, 98%), 274 (Mþ, 11), 259 (50), 181 (24), 155 (22), 154 (73), 153 (85), 152 (27), 139 (16), 138 (33), 137 (100),
136 (50), 135 (36), 124 (22), 123 (25)
11a
208 (M-4, 10%), 170 (13), 166 (58), 154 (15), 153 (62), 152 (34), 151 (29), 137 (30), 127 (25), 125 (32), 124 (27), 112 (37), 111 (26),
110 (26), 109 (100), 97(20), 95 (27)
11b
11c
11d
11e
240 (M, 6%), 170 (21), 154 (13), 153 (91), 152 (70), 137 (34), 127 (12), 125 (22), 124 (38), 123 (12), 112 (23), 111 (13), 109 (100), 107 (13)
268 (M, 4%), 170 (14), 153 (61), 152 (45), 137 (22), 125 (13), 124 (28), 109 (61), 99 (100)
268 (M, 6%), 170 (21), 154 (18), 153 (100), 152 (65), 137 (30), 125 (20), 124 (45), 109 (83), 99 (98)
275 (M þ 1, 77%), 274 (M, 17), 153 (100), 152 (41), 124 (11)
RESULTS AND DISCUSSION
Table 6. Solvents Used for Bioassays of Test Compounds
compound
solvent
Pre-emergence Bioassays. Data from pre-emergence bioassays
for radish and ryegrass seeds with both cineole compounds, their
derivatives and the carboxylic acids corresponding with the ester
derivatives are shown in Tables 7, 8 and 9. To facilitate compar-
isons between the substances their activity relative to 1,8-cineole
was determined (Table 9).
A dose-response was observed toward the radish for all com-
pounds and the eucalyptus oil showing suppression of germina-
tion, and root and shoot growth increasing with concentration.
Figures 3 and 4 give typical dose-response curves for selected
compounds (see Supporting Information for remaining dose-
response curves). A one-way ANOVA gave the concentration at
which suppression of germination, and root and shoot lengths
were significant (at P = 0.05) (Table 7).
No trends are apparent in the toxicity of these substances
against radish. The results for the pre-emergence bioassays on
radish do not support the hypothesis that the cineole esters would
have improved phytotoxicity compared to the corresponding
hydroxylated cineole and carboxylic acid, nor do they support
the hypothesis that increasing lipophilicity of the carboxylic acid
portion of the ester would improve herbicidal activity.
acetic acid
water
benzoic acid
butanoic acid
hexanoic acid
trichloromethane (chloroform)
water
hexane
t-butylacetic acid
1,8-cineole 3
hexane: chloroform; 99:1
Tween 80 in water (0.34 g L-1
Tween 80 in water (0.34 g L-1
hexane
)
)
eucalyptus oil
cinmethylin 5
3-oxo-1,8-cineole 6
hexane
hexane
3-exo-hydroxy-1,8-cineole 7
3-exo-acetoxy-1,8-cineole 8a
3-exo-butoxy-1,8-cineole 8b
3-exo-hexoxy-1,8-cineole 8c
3-exo-t-butylacetoxy-1,8-cineole 8d
3-exo-benzoxy-1,8-cineole 8e
2-endo-hydroxy-1,8-cineole 9
2-exo-hydroxy-1,4-cineole 10
2-exo-acetoxy-1,4-cineole 11a
2-exo-butoxy-1,4-cineole 11b
2-exo-hexoxy-1,4-cineole 11c
2-exo-t-butylacetoxy-1,4-cineole 11d
2-exo-benzoxy-1,4-cineole 11e
hexane
hexane
hexane
chloroform
chloroform
hexane:chloroform, 99:1
hexane:chloroform, 9:1
hexane
hexane
hexane
hexane:chloroform, 9:1
chloroform
All the carboxylic acids suppressed radish germination, root and
shoot growth at 0.1 mol L-1 or less (Table 7) and gave complete
inhibition above 0.1 mol L-1 (Table 8). Eucalyptus oil and 1,8-cineole
both suppressed germination, root and shoot growth at similar con-
centrations (Table 7) but at the higher concentration of 0.1 mol L-1
1,8-cineole was more active (Tables 8 and 9). When considering the
concentration at which suppression of germination, root and shoot
growth first occur, of the 1,8-cineole derivatives 3-oxo-1,8-cineole
was the most effective against radish with the acetate being the most
Experimental Design and Data Analysis. At each concentration
and for controls, five replicates were used and Petri dishes were placed in a
completely randomized manner in the support tray. After 72 h the number
of seeds germinating was counted and the lengths of their shoots and roots
were measured.
Data were subjected to one way analysis of variance (ANOVA), using
the SPSS 15.0 statistics package (SPSS Inc., 2007). Means were considered
to be statistically different at P = 0.05.

10152 J. Agric. Food Chem., Vol. 58, No. 18, 2010
Barton et al.
Table 7. Concentration (mol L-1) above Which Suppression of Radish and Ryegrass Occurred (at P = 0.05)
radish
ryegrass
shoot
compound
root
shoot
germination
0.1
0.1
root
0.01
germination
acetic acid
0.1
0.1
0.01
0.01
0.1
0.1
1
0.01
0.0001
0.1
0.1
benzoic acid
butanoic acid
hexanoic acid
0.01
0.01
0.001
0.01
1
0.0001
0.01
0.0001
0.001
0.1
0.01
0.01
0.01
0.01
0.1
0.1
0.1
0.0001
0.001
0.1
t-butylacetic acid
1,8-cineole 3
eucalyptus oila
3-oxo-1,8-cineole 6
0.1
0.1
0.154
0.01
0.01
0.01
0.1
0.154
0.01
0.1
1
0.0154
0.01
0.0154
0.1
0.1
0.0154
0.0001, 0.1 not 0.001 and 0.01
0.0154
0.1
0.1
3-exo-hydroxy-1,8-cineole 7
3-exo-acetoxy-1,8-cineole 8a
3-exo-butoxy-1,8-cineole 8b
3-exo-hexoxy-1,8-cineole 8c
3-exo-t-butylacetoxy-1,8-cineole 8d
3-exo-benzoxy-1,8-cineole 8e
2-endo-hydroxy-1,8-cineole 9
cinmethylin 5
0.1
0.01
0.01
0.1
0.1
0.1
0.1
0.1
1
0.1
0.01
0.01
0.01
0.01
0.01
0.1
0.01
0.01
0.001
0.1
0.01
not suppressed
0.1
0.1
not suppressed
0.1
0.1
0.01
0.01
0.0001
0.1
1
0.01
0.1
0.1
0.1
0.01, 0.1 but not 1
0.1
0.01
1
0.1
2-exo-hydroxy-1,4-cineole 10
2-exo-acetoxy-1,4-cineole 11a
2-exo-benzoxy-1,4-cineole 11e
2-exo-hexoxy-1,4-cineole 11c
2-exo-butoxy-1,4-cineole 11b
2-exo-t-butylacetoxy-1,4-cineole 11d
0.01
0.01
0.1
0.01
0.0001
0.1
0.1
0.1
0.01
0.01
0.1
0.01
0.01
0.1
0.01
not suppressed
0.1 but not 1
0.1
0.0001
0.1
0.01
0.1
0.01
0.001
0.01
0.01
0.1
0.1
0.1
0.1
a Concentration of eucalyptus oil is in g mL-1 with 0.0154 g mL-1 giving a 1,8-cineole concentration of approximately 0.1 mol L-1
.
Table 8. Pre-emergence Herbicidal Activity of Compounds Tested against
Radish and Ryegrass at 0.1 mol L-1 (Ordered on Germination Inhibition of
Radish)
Table 9. Pre-emergence Herbicidal Activity of Test Compounds against
Radish and Ryegrass at 0.1 mol L-1 Relative to 1,8-Cineole (CI = Complete
Inhibition) (Ordered on Germination Inhibition of Radish)
percentage of control
activity relative to 1,8-cineole
radish
ryegrass
radish
ryegrass
RLa SLa germa RLa SLa germa
compound
RLa SLa germa RLa SLa germa
compound
acetic acid
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
9
0
acetic acid
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
CI
benzoic acid
butanoic acid
hexanoic acid
0
0
benzoic acid
butanoic acid
hexanoic acid
CI
CI
0
0
CI
CI
0
0
CI
CI
t-butylacetic acid
0
6.7
0
t-butylacetic acid
CI
CI
2-exo-butoxy-1,4-cineole 11b
3-exo-hydroxy-1,8-cineole 7
2-endo-hydroxy-1,8-cineole 9
2-exo-hydroxy-1,4-cineole 10
2-exo-acetoxy-1,4-cineole 11a
3-oxo-1,8-cineole 6
9.3
2.6
2-exo-butoxy-1,4-cineole 11b
3-exo-hydroxy-1,8-cineole 7
2-endo-hydroxy-1,8-cineole 9
2-exo-hydroxy-1,4-cineole 10
2-exo-acetoxy-1,4-cineole 11a
3-oxo-1,8-cineole 6
CI
3.3 3.2
1.3 2.8
0.6 1.8
3.7 1.2
3.2
11.6
0.6
1.4
CI
26.8 46.5
6.8
9.9 41.7
2.7
20.5 29.3
29.2 64.3b 18.9
2.4 16.6 10.2
1.4 1.4
5.5 CI
3.7 1.6
3.5 CI
1.8 2.2
1.3 1.0
0.5 0.7
1.0 1.0
14.2
13.1
13.1
7.5
3.4
1.8
1.1
1.0
0.8
0.7
0.7
0.6
0.6
0.4
0.4
0.3
0
2.6 39.5 15.4 51.5
2.6
4.5
6.1 23.1 21.7
0
0
0
0
CI
CI
10
18.9 18.2 33.3
7.6 21.3 34.1
1.2 1.6
2.9 1.3
0.3 0.6
1.0 1.0
0.9
0.9
0.3
1.0
3-exo-acetoxy-1,8-cineole 8a
3-exo-acetoxy-1,8-cineole 8a
3-exo-t-butylacetoxy-1,8-cineole 8d
1,8-cineole 3
3-exo-t-butylacetoxy-1,8-cineole 8d 72.5 90.9
1,8-cineole 3 37.1 64.7
2-exo-t-butylacetoxy-1,4-cineole 11d 55.8 71.2
31.4 64.9 44.8 97.8
34.1 22.4 28.4 30.2
42.9
2-exo-t-butylacetoxy-1,4-cineole 11d 0.7 0.9
3-exo-hexoxy-1,8-cineole 8c
3-exo-butoxy-1,8-cineole 8b
2-exo-hexoxy-1,4-cineole 11c
eucalyptus oilc
39.8 73.3
26.7 63.4
44.4 44.3
47.7 80.4
54.7 64
47.2 16
51.4 7.9 11.1 14.6
10.2
2.3
3-exo-hexoxy-1,8-cineole 8c
3-exo-butoxy-1,8-cineole 8b
2-exo-hexoxy-1,4-cineole 11c
eucalyptus oilb
0.9 0.9
1.4 1.0
0.6 1.5
0.8 0.8
0.7 1.0
0.8 1.0
0.8 1.1
1.4 2.8
2.8 2.6
2.1 3.1
0.9 1.2
0.8 1.2
13.1
2.1
7.0
6.2
0.7
58.1 10.9 9.2
58.8 26.2 23.8
4.3
4.9
2-exo-benzoxy-1,4-cineole 11e
cinmethylin 5
3-exo-benzoxy-1,8-cineole 8e
82.9 28
85.7
23.7 46.3
2-exo-benzoxy-1,4-cineole 11e
cinmethylin 5
3-exo-benzoxy-1,8-cineole 8e
36.5 62.5
42.4 61
98
10.9 41.6 82.2
2.1 0.7
0.4
a RL = root length; SL = shoot length; germ = germination. b Italicized font = not
significant. c Concentration of eucalyptus oil is 0.0154 g mL-1 giving 1,8-cineole
a RL = root length; SL = shoot length; germ = germination. b Concentration of
eucalyptus oil is 0.0154 g mL-1 giving a 1,8-cineole concentration of approximately
concentration of approximately 0.1 mol L-1
.
0.1 mol L-1
.
active 1,4-cineole derivative (Table 7). However, at 0.1 mol L-1 the
most active of the cineole compounds against radish was 2-exo-
butoxy-1,4-cineole, being completely inhibitory (Table 8). At this
concentration the most effective pre-emergence compounds (that is,
compounds preventing germination) were 2-exo-butoxy-1,4-cineole,
3-exo-hydroxy-1,8-cineole, 2-endo-hydroxy-1,8-cineole, 2-exo-hydroxy-
1,4-cineole and 2-exo-acetoxy-1,4-cineole, with germination sup-
pressed by approximately 97% as compared to 66% suppres-
sion by 1,8-cineole (Tables 8 and 9). 2-endo-Hydroxy-1,8-cineole
was the most active of the 1,8-cineole derivatives at 0.1 mol L-1
,
being completely inhibitory of shoot growth and second only to
2-exo-butoxy-1,4-cineole in its suppression of root growth.

Article
J. Agric. Food Chem., Vol. 58, No. 18, 2010 10153
Figure 3. Effects of (a) 1,8-cineole, (b) 3-exo-acetoxy-1,8-cineole, (c) 3-exo-hexoxy-1,8-cineole, (d) 2-exo-acetoxy-1,4-cineole, (e) 2-exo-butoxy-1,4-
cineole and (f) eucalyptus oil on root growth, shoot growth and germination of radish 72 h after exposure. Bars = (SE.
In general the 1,8-cineole derivatives were more effective against
radish roots than shoots while 1,4-cineole derivatives showed no
particular trend in their activity against roots versus shoots (Tables 7
and 8). Considering germination and root and shoot suppres-
sion together, 3-exo-acetoxy-1,8-cineole was the most active of the
1,8-cineole esters, although only the hexanoate ester gave complete
suppression of germination (at 1 mol L-1) (Figure 3). Although the
Again, as for the radish, ryegrass germination, root and shoot
growth were suppressed by the acids at 0.1 mol L-1 or less
(Table 7) and germination was completely inhibited by the acids
above 0.1 mol L-1 (Table 8).
Eucalyptus oil and 1,8-cineole first suppressed ryegrass germi-
nation, root and shoot growth at similar concentrations of 0.0154 g
mL-1/0.1 mol L-1 (Table 7) and while their suppression of
shoot growth and root growth were similar, eucalyptus oil was
approximately six times more effective at suppressing germina-
tion than 1,8-cineole (Tables 8 and 9), a contrast to what was
observed for the radish where 1,8-cineole was more active. Over-
all, when considering the concentration at which suppression first
occurs, 3-exo-hexoxy-1,8-cineole was the most active 1,8-cineole
derivative against ryegrass but of the 1,8-cineole derivatives,
3-exo-t-butylacetoxy-1,8-cineole suppressed ryegrass shoot
growth at a lower concentration than the other 1,8-cineole
derivatives. Its suppression did not go above 60% until complete
inhibition at 1 mol L-1 (Figure 4). Of the 1,4-cineole derivatives,
the most effective germination inhibitor was 2-exo-acetoxy-1,4-
cineole. Although 2-exo-benzoxy-1,4-cineole only inhibited germina-
tion at 1 mol L-1, it suppressed ryegrass root and shoot growth
at a lower concentration than any of the cineole derivatives
butoxy ester of 1,4-cineole gave complete inhibition at 0.1 mol L-1
,
2-exo-acetoxy-1,4-cineole gave suppression at a lower concentration
and overall was the most effective of the 1,4-cineole esters (Figure 3).
Ryegrass also showed a dose response toward all compounds
and eucalyptus oil in the pre-emergence bioassays, with suppres-
sion of germination, root growth and shoot growth increasing
with concentration. A one way ANOVA gave the concentration
at which suppression of germination, and root and shoot lengths
were significant (at P = 0.05) (Table 7).
As for radish, there are no trends in the toxicity of these
substances against ryegrass. The phytotoxicity of the esters is no
better than that of the corresponding hydroxylated cineole and
carboxylic acid in the ryegrass pre-emergence bioassays. Neither
did increasing the lipophilicity of the carboxylic acid portion of
the ester improve herbicidal activity against ryegrass.

10154 J. Agric. Food Chem., Vol. 58, No. 18, 2010
Barton et al.
Figure 4. Effects of (a) 1,8-cineole, (b) 3-exo-hexoxy-1,8-cineole, (c) 3-exo-t-butylacetoxy-1,8-cineole, (d) 2-exo-acetoxy-1,4-cineole, (e) 2-exo-benzoxy-
1,4-cineole and (f) eucalyptus oil on root growth, shoot growth and germination of ryegrass 72 h after exposure. Bars = (SE.
(Figure 4). In general, all the substances were more effective at
suppressing ryegrass root and shoot growth than they were
at suppressing its germination but there was no clear trend in
the sensitivity of ryegrass roots compared to ryegrass shoots
(Table 7).
at 0.1 mol L-1. In radish, the 2- and 3-hydroxy-cineole com-
pounds had similar germination suppression at 0.1 mol L-1 while
for ryegrass 2-endo-hydroxy-1,8-cineole was less effective against
germination than the other hydroxy-cineole compounds. Like-
wise, a comparison of 3-exo-hydroxy-1,8-cineole, 2-endo-hydroxy-
1,8-cineole and 2-exo-hydroxy-1,4-cineole shows there was no
effect of position of functionalization on activity at concentra-
tions when initial suppression was observed (Table 7).
In conclusion, hydroxy and ester derivatives of 1,8-cineole and
1,4-cineole have a dose-dependent herbicidal activity against
annual ryegrass and radish germination and root and shoot
growth, although no trends were observed between lipophilicity
of ester derivatives and herbicidal activity. In addition many of
the derivatives have improved phytotoxicity relative to 1,8-
cineole. A likely contributor to their phytotoxicity is hydrolysis
of the esters on uptake by the plants to produce the hydroxy-
cineole and carboxylic acid. The carboxylic acid may be phyto-
toxic due to a generalized pH effect. Weak organic acids with a
pH between 5 and 8 can disturb photosynthetic processes by
disrupting the hydrogen ion concentration gradient across the
At 0.1 mol L-1, 2-exo-acetoxy-1,4-cineole was the most effec-
tive of the cineole compounds as a pre-emergence herbicide
against ryegrass giving complete inhibition of germination
(Table 8). In contrast to radish, 2-endo-hydroxy-1,8-cineole was
less active against ryegrass roots, shoots and germination than
3-exo-hydroxy-1,8-cineole.
For radish, root sensitivity was higher than shoot sensitivity for
most of the tested substances at 0.1 mol L-1, but there was no
strong trend in sensitivity of ryegrass roots versus ryegrass shoots.
A comparison of the germination inhibition at 0.1 mol L-1 does
not indicate a greater sensitivity of one species over another, but
ryegrass roots and shoots were generally more sensitive to the
cineole compounds at 0.1 mol L-1 than were the radish roots and
shoots. No effect of functionalizion of the cyclohexane ring at
position 2 compared to position 3 was observed for either species

Article
J. Agric. Food Chem., Vol. 58, No. 18, 2010 10155
two sides of the thylakoid membrane (22). Future experiments
should focus on the bioactivity of compounds relative to 1,8-
cineole in field tests as well as experiments to assess whether these
esters hydrolyze on uptake by plants.
(10) Muller, C. H.; Muller, W. H.; Haines, B. L. Volatile growth
inhibitors produced by aromatic shrubs. Science 1964, 143, 471–473.
(11) Halligan, J. P. Toxic terpenes from Artemisia california. Ecology
1975, 56, 999–1003.
(12) Kumar, N.; Motto, M. G. Volatile constituents of peony flowers.
Phytochemistry 1986, 3, 663–671.
(13) Angelini, L. G.; Carpanese, G.; Cioni, P. L.; Morelli, I.; Macchia,
M.; Flamini, G. Essential oils from Mediterranean Lamiaceae as
weed germination inhibitors. J. Agric. Food Chem. 2003, 51,
6158–6164.
Supporting Information Available: Additional dose-response
curves. This material is available free of charge via the Internet at
http://pubs.acs.org.
(14) Heisey, R. M.; Delwiche, C. C. Phytotoxic volatiles from
Trichostema lanceolatum. Am. J. Bot. 1984, 71, 821–828.
(15) Romagni, J.; Allen, S.; Dayan, F. Allelopathic effects of volatile
cineoles on two weedy plant species. J. Chem. Ecol. 2000, 26 (1),
303–313.
(16) Romagni, J.; Duke, S.; Dayan, F. Inhibition of Plant Asparagine
Synthetase by Monoterpene Cineoles. Plant Physiol. 2000, 123,
725–732.
(17) Romagni, J.; Duke, S.; Dayan, F., Retraction - Inhibition of Plant
Asparagine Synthetase by the Monoterpene Cineole. Volume 123
(2000), pp.725-732. Plant Physiol. 2005, 137, 1487.
(18) de Boggiatto, M.; de Heluani, C.; de Fenik, I.; Catalan, C. Regios-
pecific Functionalization of the Monoterpene Ether 1,3,3-Trimethyl-
2-oxabicyclo[2.2.2]octane (1,8-Cineole). Synthesis of the Useful
Bridged γ-Lactone 1,3-Dimethyl-2-oxabicyclo[2.2.2]octan-3f5-olide. J.
Org. Chem. 1987, 52, 1505–1511.
LITERATURE CITED
(1) Appleby, A. P.; Muller, F.; Carpy, S., Weed control. In Agrochem-
icals; Muller, F., Ed.; Wiley-VCH: New York, 2000; pp 687-709.
(2) Pimentel, D.; McNair, S.; Janecka, J.; Wightman, J.; Simmonds, C.;
O’Connell, C.; Wong, E.; Russel, J.; Zern, T.; Aquino, T.; Tsomondo,
T. Economic and environmental threats of alien plant, animal, and
microbe invasions. Agric., Ecosyst. Environ. 2001, 84, 1–20.
(3) Balandrin, M. F.; Klocke, J. A.; Wurtele, E. S.; Bollinger, W. H.
Natural plant chemicals: sources of industrial and medicinal materi-
als. Science 1985, 228 (4704), 1154–1160.
(4) Duke, S. O.; Romagni, J.; Dayan, F. Natural products as sources
for new mechanisms of herbicidal action. Crop Prot. 2000, 19,
583–589.
(5) Duke, S.; Dayan, F.; Romagni, J.; Rimando, A. M. Natural
products as sources of herbicides: current status and future trends.
Weed Sci. 2000, 40, 99–111.
(19) Payne, G. P. Preparation of 2-exo-Hydroxy-7-oxabicyclo[2.2.1]-
(6) Cornes, D. In Callisto: a very successful maize herbicide inspired
by allelochemsitry; Proceedings of the 4th World Congress on Allelo-
pathy, “Establishing the Scientific Base”, Charles Sturt University,
Wagga Wagga, New South Wales, Australia., 2005; Harper, J., An, M.,
Wu, H., Kent, J., Eds.; The Regional Institute Limited: Charles Sturt
University: Wagga Wagga, New South Wales, Australia, 2005;
pp 569-572.
(7) Apsland, R. O. Monoterpenes: relationship between structure and
inhibition of germination. Phytochemistry 1968, 7, 1995–1997.
(8) Muller, W. H.; Muller, C. H. Volatile growth inhibitors produced by
Salvia species. Bull. Torrey Bot. Club 1964, 91, 327–330.
(9) Vaughn, S.; Spencer, G. Volatile Monoterpenes as Potential Parent
Structures for New Herbicides. Weed Sci. 1993, 41, 114–119.
heptanes. US Patent 4,487,945, 1984.
(20) Silvestre, A.; Cavaleiro, J.; Feio, S.; Roseiro, J.; Delmond, B.;
Filliatre, C. Synthesis of Some New Benzylic Ethers from 1,8-Cineole
with Antimicrobial Activity. Monatsh. Chem. 1999, 130, 589–595.
(21) Luzzio, F., A; Duveau, D., Y , Enzymatic resolution of the 1,3,3-
trimethyl-2-oxabicyclo[2.2.2]octane (1,8-cineole) system. Tetrahe-
dron: Asymmetry 2002, 13, 1173–1180.
(22) Stenersen, J. Chemical pesticides: mode of action and toxicology,
1st ed.; CRC Press: Boca Raton, FL, 2004.
Received for review May 12, 2010. Revised manuscript received August 4,
2010. Accepted August 9, 2010.