Combined strategy for phytotoxicity enhancement of benzoxazinones

Article abstract of DOI:10.1021/jf903445m

Fifteen new derivatives of D-DIBOA, including aromatic ring modifications and the addition of side chains in positions C-2 and N-4, were synthesized and their phototoxicity, selectivity, and structure-activity relationships evaluated. The most active comp

Full text of DOI:10.1021/jf903445m

J. Agric. Food Chem. 2010, 58, 2047–2053 2047
DOI:10.1021/jf903445m
Combined Strategy for Phytotoxicity Enhancement of
Benzoxazinones
´
F
RANCISCO A. MACIAS,* NURIA
AVID
C
HINCHILLA, ELENA
´
A ,
RROYO, JOSEꢀ M. G. MOLINILLO
D
M
ARIN
,
AND
ROSA M. VARELA
ꢀ
ꢀ
Allelopathy Group, Department of Organic Chemistry, University of Cadiz, Avda. Republica Saharaui,
ꢀ
s/n, 11510 Puerto Real, Cadiz, Spain
Fifteen new derivatives of D-DIBOA, including aromatic ring modifications and the addition of side
chains in positions C-2 and N-4, were synthesized and their phytotoxicity, selectivity, and
structure-activity relationships evaluated. The most active compounds among the derivatives at
the C-2 position were 6-Cl-2-Et-D-DIBOA and 6-F-2-Et-D-DIBOA. Of the derivatives at N-4, the
most active compounds were 6-Cl-4-Pr-D-DIBOA and 6-Cl-4-Val-D-DIBOA. These four compounds
showed high levels of inhibition in root length at very low concentrations in all species. The most
remarkable result is the 70% inhibition observed for the root length of cress at 100 nM caused by the
latter two compounds. These results support our previous research and conclusions regarding the
steric, electronic, and solubility requirements to achieve the maximum phytotoxic activity.
KEYWORDS: Benzoxazinoids; phytotoxicity; QSAR; herbicides; SAR
INTRODUCTION
synthetic benzoxazinones 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-
one (D-DIBOA) and 4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one
(ABOA) were found to be the most phytotoxic benzoxazinones
of those with the closest analogy to the natural products (Figure 1).
On the basis of these results, structural modifications were
planned, and a structure-activity relationship study of several
modified benzoxazinones was carried out. On the one hand, the
systematic esterification of D-DIBOA at the N-4 position re-
sulted in a new generation of esters with increased lipophilicity.
These compounds showed more marked phytotoxic effects and
higher selectivity in comparison to natural benzoxazinones (8,9).
In addition, the absence of a hydroxyl group at position C-2 was
found to have a crucial influence on phytotoxicity, in contrast to
other previously evaluated bioactivities, including algicide and
fungistatic properties (10). On the other hand, the addition of
alkyl groups at position C-2 also gave rise to an increase in
bioactivity. In both cases the improvements were attributed to a
modification of the transport phenomena necessary for the
phytotoxic action of the tested chemicals in the context of the
Tice model for agrochemical design (11).
Natural products based on the (2H)-1,4-benzoxazin-3(4H)-one
system have been prominent in the field of phytochemistry re-
search for decades, since the first isolation of 2,4-dihydroxy-(2H)-
1,4-benzoxazin-3(4H)-one (DIBOA) and 2,4-dihydroxy-7-meth-
oxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) from maize (1)
(Zea mays L.) and barley (2) (Secale cereale L.), respectively. Since
these early days, the interesting bioactivity of these compounds has
encouraged research into natural products and modified deriva-
tives as potential biopesticides (3) among other applications. The
development of pesticides from natural products is believed to
provide new modes of action and a more specific interaction with
the pest and to be more environmentally friendly (4). The technical
and economic optimization of bioactive chemical production has
encouraged traditional research on natural bioactive agents with
the aim of simplifying the natural structure. In most cases,
however, this leads to loss of the bioactivity. The current trend
of using a natural product structure as a template to obtain new
leads in the discovery of bioactive molecules is greatly exemplified
by the research on phytotoxic benzoxazinones.
Moreover, an improvement in the benzoxazinone skeleton
through modification of steric and electronic features was devel-
oped (12, 13). These modifications included the addition of
halogen substituents to the aromatic ring. Optimal ranges for
molecular volume, dipole moment, and polarizability of the
benzoxazinones for the maximum phytotoxic activity were char-
acterized. The synthetic routes used to obtain these new deriva-
tives are easier to develop and scale-up than those used for natural
benzoxazinones substituted at C-2. Benzoxazinones are therefore
a rare example in which the simplification of a natural structure
leads to increased bioactivity.
Among the studies on benzoxazinones performed to date, some
concern the elucidation of structure-activity relationships of
several modified benzoxazinones. The primary objective of these
studies was to optimize the molecular functionalization to achieve
the maximum phytotoxicity, as detailed in the recent reports
on the phytotoxicity of benzoxazinones and their direct degra-
dation products on various plant species, including common
crops (5) and problematic weeds (6, 7). The results of this research
show that the relative activity to the crop or weed is maintained for
each of the benzoxazinone modification patterns studied. The
As a final part of these studies, and considering the promising
results obtained for some of the derivatives, the synthesis and
*To whom correspondence should be addressed. Phone: þ34-
956.016.365. Fax: þ34-956.016.193. E-mail: famacias@uca.es.
© 2009 American Chemical Society
Published on Web 12/16/2009
pubs.acs.org/JAFC

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Macıas et al.
2048 J. Agric. Food Chem., Vol. 58, No. 3, 2010
of starting material). Sodium borohydride (2 mol equiv) was
added, and the solution was vigorously stirred. A solution of the
nitrophenoxyacetate in 1,4-dioxane (0.5 g/mL) was added drop-
wise to this stirred suspension. The progress of the reaction was
monitored by TLC. Once the reaction was complete, the suspen-
sion was vacuum filtered through Celite to remove the catalyst,
and the filtrate was treated with 10% HCl until pH = 2 was
reached. This solution was further extracted with ethyl acetate
(ꢀ3). The organic layers were combined and dried over anhy-
drous sodium sulfate, and the solvent was distilled under reduced
pressure. The resulting residue was purified by column chroma-
tography (CC; SiO2, ethyl acetate/hexane, increasing polarity) to
give the corresponding benzoxazinone (Figure 2).
General Procedure for Esterification. The appropriate D-
DIBOA halo derivative (100 mg) was dissolved in dry pyridine
(25 mL), and 1.2 mol equiv of the appropriate acyl chloride
(commercial) was added dropwise at 0 °C (ice bath) under a dry
argon atmosphere. The reaction mixture was allowed to warmp to
room temperature; 12 h later, EtOAc (25 mL) was added, and the
mixture was transferred to an extraction funnel and washed with
0.1 N HCl (3 ꢀ 50 mL) and 0.1 N NaHSO4 (3 ꢀ 50 mL). The
organic phases were further combined and dried over anhydrous
magnesium sulfate. The solvent was removed (rotatory evapora-
tor), and the residue was chromatographed (CC; SiO2, EtOAc/
hexane, 1:10) to give the benzoxazinone ester derivatives (Figure 3).
Calculation of IC50 and LogP. The phytotoxicity data were
fitted to a sigmoidal dose-response model (constant slope) by
employing the GraphPad Prism v.4.00 software package
(GraphPad Software Inc.). cLogP values were estimated using
the OSIRIS property explorer (ChemExper Inc.). This software
uses the Chou and Jurs algorithm, which is based on computed
atom contributions (16).
Figure 1. Structures of 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-
DIBOA) and 4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one (ABOA).
bioactivity evaluation of models including more than one kind of
structural modification were planned. The main objective of this
research was to achieve the maximum phytotoxic effects in
different standard target species. As a first approach, the bioac-
tivity of these novel leads on common crops selected as standard
target species is reported herein.
Fifteen derivatives were synthesized, and these included aro-
matic ring modifications plus the addition of side chains in
positions C-2 and N-4 (Tables 1 and 2). These compounds were
evaluated in terms of the phytotoxicity results, selectivity, and
structure-activity relationships, and the results are summarized
below.
MATERIALS AND METHODS
General Experimental Procedures. The purities of the com-
1
pounds to be tested were determined by H NMR and HPLC
analyses and were found to be >98%. 1H and 13C NMR spectra
were recorded using CDCl3 as solvent on a Varian INOVA
spectrometer at 399.99 and 100.577 MHz, respectively. The
resonance of residual chloroform was set to δ 7.25. The solvent
peak for 13C was set to δ 77.00 (chloroform), and this was used as
the internal reference. UV-vis spectra were obtained using a
Varian Cary 50 BIO spectrophotometer with chloroform as the
solvent. Mass spectra (EIMS) were recorded using a Voyager
Thermoquest spectrometer. FTIR spectra were obtained on a
Perkin-Elmer Spectrum BX FTIR system. Frequency values are
Molecular Modeling and QSAR Calculations. Three-dimen-
sional models of the tested chemicals were obtained from AM1
calculations performed by Hyperchem 7.01 software (Hypercube
Inc.). Dipole moments, partial charges, polarizabilities, and
molecular volumes were obtained by employing the algorithms
implemented in this software. Molecular parameter/activity cor-
relations were performed using Microsoft Office Excel 2007
spreadsheets (Microsoft Corp.).
given in cm-1
.
Preparation of Derivatives. The chemicals were obtained ac-
cording to the previously mentioned methodology, by a sequence
of nucleophilic substitution (side chain linkage), reductive cycli-
zation (benzoxazinone ring formation), and esterification for the
N-4 derivatives. The starting materials employed were 2-nitro-
phenols substituted at the appropriate positions: 4-fluoro-2-
nitrophenol, 4-chloro-2-nitrophenol, and 2-chloro-2-nitrophe-
nol. These compounds were purchased from Sigma-Aldrich Co.
General Procedure for Nucleophilic Substitution. The start-
ing halo-2-nitrophenol was dissolved in a 0.1 M solution of KOH
in absolute ethanol (1 mol equiv of KOH). After 1 h, the solvent
was removed under reduced pressure. The resulting alkoxide was
redissolved in DMF (50 mL/g of starting material), and 1.2 mol
equiv of the appropriate 2-halo ester was added. The reaction
mixture was stirred under argon for 24 h. After this time, ethyl
acetate (50 mL/g of starting material) was added, and the
resulting organic solutions were washed with five portions of
distilled water. The organic layers were combined and dried over
anhydrous sodium sulfate, and the solvent was distilled under
reduced pressure. The crude product was purified by column
chromatography (CC; SiO2, ethyl acetate/hexane, 20:80) to give
ethyl 2-(20-nitrophenoxy)acetates in quantitative yield (Figure 2).
General Procedure for Reductive Cyclization. Pd/C (10%
Pd, 10% w/w with respect to starting nitrophenoxyacetate) was
suspended in an aqueous solution of 1,4-dioxane (1:1) (100 mL/g
Phytotoxicity Bioassays. Target Plants. The selection of tar-
get plants was based on an optimization process carried out by us
in the search for a standard phytotoxicity evaluation bioassay
(19). This process led to several standard target species (STS)
being proposed, including monocot Allium cepa L. (onion) and
dicots Lycopersicon esculentum Will. (tomato), Lepidium sativum
L. (cress), and Lactuca sativa L. (lettuce), which were assayed for
this study.
Methodology. Bioassays were carried out using Petri dishes
(90 mm diameter) with one sheet ofWhatman No. 1 filterpaper as
the substrate. Germination and growth were conducted in aqueous
solutions at controlled pH using 10-2 M 2-(N-morpholino)ethane-
sulfonic acid (MES) and the addition of 1 M NaOH to give a pH of
6.0. Solutions (0.2, 0.1, 0.02, 0.01, and 0.002 M) of the compounds
to be assayed were prepared in DMSO and then diluted with buffer
(5 μL of DMSO/mL of buffer) to give the test concentrations for
each compound (1, 0.5, 0.1, 0.05, and 0.01 mM). This procedure
facilitated the solubility of the assayed compounds. The number of
seeds was 25 in each Petri dish. The treatment control (or internal
reference solution) (5 mL) was added to each Petri dish. Four
replicates were used for each species.
After the addition of seeds and aqueous solutions, Petri dishes
were sealed with Parafilm to ensure closed-system models. Seeds
were further incubated at 25 °C in a Memmert ICE 700 con-
trolled-environment growth chamber in the absence of light.

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J. Agric. Food Chem., Vol. 58, No. 3, 2010 2049
Table 1. Derivatives Prepared with Functionalization at C-2
R1
R2
R3
R4
compound
F
H
-CH2CH3
-CH2CH2CH3
C6H5
H
H
H
H
H
H
H
H
H
H
H
2-ethyl-6-fluoro-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
6-fluoro-4-hydroxy-2-propyl-(2H)-1,4-benzoxazin-3(4H)-one
2-phenyl-6-fluoro-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
2-ethoxycarbonyl-6-fluoro-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
2-ethyl-6-chloro-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
6-chloro-4-hydroxy-2-propyl-(2H)-1,4-benzoxazin-3(4H)-one
6-chloro-2-phenyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-2-ethyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-4-hydroxy-2-propyl-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-2-phenyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-2-ethoxycarbonyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one
F
H
F
H
F
H
EtOCO
Cl
Cl
Cl
H
H
H
H
H
-CH2CH3
-CH2CH2CH3
C6H5
H
H
Cl
Cl
Cl
Cl
-CH2CH3
-CH2CH2CH3
C6H5
EtOCO
Table 2. Derivatives Prepared with Functionalization at N-4
R1
R2
R3
R4
compound
F
H
H
H
H
H
H
H
H
-COCH2CH3
-CO(CH2)3CH3
-COCH2CH3
-CO(CH2)3CH3
-COCH2CH3
-CO(CH2)3CH3
6-fluoro-4-propionyloxy-(2H)-1,4-benzoxazin-3(4H)-one
6-fluoro-4-valeroyloxy-(2H)-1,4-benzoxazin-3(4H)-one
6-chloro-4-propionyloxy-(2H)-1,4-benzoxazin-3(4H)-one
6-chloro-4-valeroyloxy-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-4-propionyloxy-(2H)-1,4-benzoxazin-3(4H)-one
8-chloro-4-valeroyloxy-(2H)-1,4-benzoxazin-3(4H)-one
F
Cl
Cl
H
H
H
H
Cl
Cl
Figure 2. General procedure for the synthesis of tested chemical functionalized at C-2.
Bioassay Data Acquisition. Evaluated parameters (germi-
nation rate, root length, and shoot length) were recorded using a
Fitomed system (16), which allowed automatic data acquisition
and statistical analysis by its associated software.
Statistical Analysis. Data were statistically analyzed using
Welch’s test, with significance fixed at 0.01 and 0.05. Results are
represented in bar charts in which the null value represents
control, negative values represent inhibition, and positive values
represent stimulation of the studied parameter (15). Phytotoxic
activities expressed in this way can be found in the Supporting
Information for all chemicals and species. Once the germina-
tion and growth data had been acquired, cluster analysis was
used to group compounds with similar phytotoxicity behavior
and associate them with their molecular structure. Complete
linkage was used as an amalgamation rule, and the distance
measurement was based on squared Euclidean distances, given by
the equation
Figure 3. General procedure for the synthesis of tested chemical functio-
nalized at N-4.
Bioassays took 4 days for cress, 5 days for lettuce and tomato, and
7 days for onion. After growth, plants were frozen at -10 °C for
24 h to avoid subsequent growth during the measurement
process. This helped in the handling of the plants and allowed a
more accurate measurement of root and shoot lengths.
The commercial herbicide Logran, a combination of N-(1,1-
dimethylethyl)-N-ethyl-6-(methylthio)-1,3,5-triazine-2,4-diamine
(terbutryn, 59.4%) and 2-(2-chloroethoxy)-N-{[(4-methoxy-6-
methyl-1,3,5-triazin-2-yl)amino]carbonyl}benzenesulfonamide
(triasulfuron, 0.6%), was used as the internal reference in accor-
dance with a comparison study reported previously (15).
X
2
dðx, yÞ ¼
ðxi -yi Þ
i
where d(x,y) is the squared Euclidean distance (i-dimensional),
i represents the number of variables, and x and y are the observed

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Macıas et al.
2050 J. Agric. Food Chem., Vol. 58, No. 3, 2010
Figure 4. Phytotoxicity effects of tested compounds on the root length of the species L. sativum L. and L. esculentum Will. According with Welch’s test,
inhibition values higher than -40% are significantly different at P < 0.01, inhibition values between -40% and -20% are significantly different at 0.01 < P <
0.05, and values between -20% and þ30% present P > 0.05.
values. The cluster was obtained using Statistica v.5.0 software
(Statsoft Inc.). Germination rate, shoot length, and root length
effects for all tested species were included in the analysis to
provide an overall view of the phytotoxicity and its relationship
with chemical structure. EC50 values were obtained after the
phytotoxicity data had been adjusted to concentration
(logarithmic scale), to a constant slope sigmoidal dose-response
curve, defined by the equation
adjustment and r2 were obtained using GraphPad Prism software
v.4.00 (GraphPad Software Inc.).
RESULTS AND DISCUSSION
General Bioactivity Profiles. All assayed compounds were
active and showed inhibitor profiles in the growth parameters
evaluated. In all cases the most affected parameter was root
length (Figures 4 and 5). The phytotoxic activity levels of these
derivatives were species dependent. Thus, in the case of cress the
most active compounds were 6-Cl-4-Val-D-DIBOA, 6-Cl-2-Et-
D-DIBOA, and 6-F-4-Pr-D-DIBOA, all ofwhich showed activity
even at concentrations below 1 μM. In the cases of onion, tomato,
and lettuce the most activecompounds were6-Cl-4-Pr-D-DIBOA
and 6-Cl-4-Val-D-DIBOA, and these showed high activities at
very low concentrations (1 and 5 μM).
Ymax -Ymin
Y ¼ Ymin
þ
50 -X
1 þ 10logEC
where X indicates the logarithm of concentration, Y indicates
the response (phytotoxicity), and Ymax and Ymin are the max-
imum and minimum values of the response, respectively. Good-
ness of fit is described by the determination coefficient (r2). The

Article
J. Agric. Food Chem., Vol. 58, No. 3, 2010 2051
Figure 5. Phytotoxicity effects of tested compounds on the root length of the species A. cepa L. and L. sativa L. According with Welch’s test, inhibition values
higher than -40% are significantly different at P < 0.01, inhibition values between -40% and -20% are significantly different at 0.01 < P < 0.05, and values
between -20% and þ30% present P > 0.05.
Derivatives at C-2. The most active compounds of this
series were 6-Cl-2-Et-D-DIBOA and 6-F-2-Et-D-DIBOA. The
first compound showed inhibition values of about 60-70%
for root length of onion and cress at a concentration 1 μM. The
second compound showed values of 50% at the same concen-
tration.
Derivatives at N-4. The most active compounds of this series
were 6-Cl-4-Pr-D-DIBOA and 6-Cl-4-Val-D-DIBOA. Both com-
pounds showed high levels of inhibition in root length at very low
concentrations in all species. For example, the inhibition of root
length for tomato and lettuce was 50% at 1 and 5 μM, whereasthe
inhibition in the case of onion was closer to 90% at the same
concentration. The most remarkable result is the 70% inhibition
observed for root length of cress at 100 nM.
groups (G1 for the highest activities and G2 for weaker effects).
G2 is divided into two subgroups (G2a for high effects and
G2b for low effects). The most active group (G1) is formed by
the derivatives 6-Cl-4Pr, 6-Cl-4-Val, 6-F-4-Pr, 6F-4-Val, 6-Cl-2-
Et, and 6-F-2-Et-D-DIBOA. It is worth pointing out that all
compounds were more active than the commercial herbicide
Logran, including those in group G2. Most compounds in-
cluded in G2 have good activity profiles, with the exception
of 6-F-2-EtCO, which is includedas the onlymember ofsubgroup
G2b.
On the basis of the cluster analysis we can analyze the data
according to the position of the functionalization. Regarding the
aromatic part of the molecule, compounds halogenated at the C-6
position are generally more active than the corresponding com-
pounds halogenated at C-8, except for derivatives with a phenyl
group at C-2, for which there is little difference between them. A
steric effect caused by the aromatic moiety could be the cause of
Quantitative Structure-Activity Relationship (QSAR). A clus-
ter analysis for growth results in the four species for all com-
pounds is shown in Figure 6. Activities can be divided in two main

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Macıas et al.
2052 J. Agric. Food Chem., Vol. 58, No. 3, 2010
Figure 6. Cluster analysis (phytotoxicity data, germination, and growth parameters, all tested species) of the tested chemicals.
Figure 7. Cluster analysis (phytotoxicity data, germination, and growth parameters, all tested species) of the N-4 and C-2 derivatives.
this result. If we analyze separately the two types of functiona-
lization (Figure 7), it can be seen from the clusters that the
behavior is maintained for both families, with the most active
compounds being halogenated at C-6. For C-2 derivatives,
the most active compounds are clearly 6-Cl-2-Et-D-DIBOA
and 6-F-2-Et-D-DIBOA. Both compounds showed highly sig-
nificant inhibition levels. For example, the derivative 6-Cl-2-
Et-D-DIBOA showed an IC50 of 400 nM (r2 = 0.9614) for
the root of cress as well as values of 2.3 μM (r2 = 0.9528) and 1.6
μM (r2 = 0.9732) for the root of tomato and onion, respectively.
Compound 6-F-2-Et-D-DIBOA exhibited an IC50 at 1 μM (r2 =
0.9838) and 1.3 μM (r2 = 0.9791) for the roots of cress and onion,
respectively.
The most active N-4 derivatives were 6-Cl-4-Pr-D-DIBOA and
6-Cl-4-Val-D-DIBOA, both of which showed IC50 values of 60
nM (r2 = 0.8957 and r2 = 0.9567) for cress and 200 nM (r2 =
0.9808 and r2 = 0.9743) for onion.
6-F-D-DIBOA, 6-Cl-D-DIBOA and 8-Cl-D-DIBOA can be
considered as reference compounds in our study (12), and it can
be seen by comparing the values of IC50 for each species (Figure 8)
that activity varies depending on the type of substitution. In
general, the modifications carried out on the N-4 position lead to
an increase in the activity levels with respect to reference com-
pounds, and this increase is greater than that generated by
changes at the C-2 position. Analysis of each of the species
individually shows that in the case of cress (L. sativum) and onion
(A. cepa) the modifications introduced do not cause a substantial
improvement in the activity. In the case of lettuce (L. sativa), the
derivative 6-F-4-Pr-D-DIBOA has enhanced activity by almost
one logarithmic unit, but the clearest effect is observed for 8-Cl-2-
Ph-D-DIBOA. Finally, for tomato (L. esculentum) the most
marked improvement in activity is observed with the derivative
6-Cl-4-Val-D-DIBOA.
The effects of the halogen substituents are clearly position-
related, as demonstratedin our previous research (8,17). The high
phytotoxic effects provoked by halogenated benzoxazinones
cannot therefore be attributed to the intrinsic toxicity of the
halogen itself but rather to the marked electronic transformation
of the molecule. Once the optimal functionalization for maximum
phytotoxicity is reached, further research to assess environmental
and nontarget organism toxicity is needed.
The bioactivity data for these chemicals match completely with
those previously recorded for the lead halo compounds: the
choice of position for functionalization and the nature of the
optimal functional group, as well as a combination of these two
factors, produce a synergistic effect on the activity values. This
supports our previous research and conclusions regarding the
steric, electronic, and solubility requirements to achieve the
maximum phytotoxic activity. These novel compounds should
also be assayed in particularly problematical weeds and the
results compared to those for strategic crops such as wheat or
rice (7, 8, 12, 17).

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J. Agric. Food Chem., Vol. 58, No. 3, 2010 2053
Figure 8. Comparison of the IC50 values (root length) of tested compounds grouped by the aromatic substitution for each species.
Supporting Information Available: (1) Complete spectro-
scopic data of synthesized compounds and (2) bioassay data on
L. sativum L., L. sativa L., L. esculentum L., and A. cepa L. This
material is available free of charge via the Internet at http://pubs.
acs.org.
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Received for review October 1, 2009. Revised manuscript received
November 25, 2009. Accepted November 26, 2009. This research was
supported by the Ministerio de Ciencia y Tecnologıa, Spain (MCYT;
Project No. AGL-2006-10570-AGR) and by Project Fellowships from
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Optimization of Benzoxazinones as Natural Herbicide Models by
Lipophilicity Enhancement. J. Agric. Food Chem. 2006, 54, 9357–
9365.
ꢀ
the Ministerio de Educacion y Ciencia, Spain (N.Ch.). The Junta de
Andalucıa, Spain (D.M.), are also gratefully acknowledged.