Previous PageTable Of ContentsNext Page

Benzoxazinoids from wheat: preparation and structure-activity relationships.

Francisco A. Macías, David Marín, Alberto Oliveros-Bastidas, David Chinchilla and José M.G. Molinillo

Grupo de Alelopatía, Departamento de Química Orgánica, Universidad de Cádiz. Facultad de Ciencias, C/ República Saharaui s/n, 11510 Puerto Real, Cádiz, Spain. Email: chema.gonzalez@uca.es

Abstract

DIMBOA and DIBOA have been described as important allelochemicals from Gramineae as well as Acanthaceae, Rannunculaceae and Scrophulariaceae plants. Several bioactivities have been described and evaluated for these compounds and their degradation products. These include fungistatic, anti-feedant and phytotoxic activities. In our ongoing studies about allelochemicals as alternative herbicide models, different amounts of starting allelochemicals and degradation products were needed for the preparation of suitable analytical standards and soil dynamic studies. Isolation and synthetic methodologies have been optimized for them.

Additionally, the obtained compounds were evaluated over Standard Target Species (Lepidium sativum L., Lycopersicon esculentum Will., Allium cepa L., and Triticum aestivum L.) and common wheat weeds (Lolium rigidum and Avena fatua L.). We have studied the structural requirements for this activity, as well as some molecular properties that can be related with the results obtained. 1,4-benzoxazinones showed high phytotoxicity levels, but the most active compound was the aminophenoxazin APO, with persistence of the effect at low concentrations.

These data suggest that the different bioactivities shown by degradation products of DIBOA and DIMBOA have to be taken into account in the research of their biological activities and mode of action, since the effects observed could be related to the presence of such derivatives in stock solutions and standards employed for these evaluations, especially in the longer time experiments.

Media summary

SAR study was made to explore the potential use of benzoxazinones as leads for herbicide models development. Their ecological role is discussed.

Keywords

Benzoxazinones, SAR, phytotoxicity, D-DIBOA, D-DIMBOA, STS.

Introduction

Benzohydroxamic acids containing a 1,4-benzoxazin moiety have been isolated from Poaceae (Barnes et al. 1987; Niemeyer et al. 1990; Zuñiga and Massardo 1991; Wu et al. 2001) and other members of Acanthaceae, Rannunculaceae and Scrophulariaceae (Niemeyer, 1998; Pratt et al. 1995). These compounds occur in plants as 2-O-β-d-glucosides (Wahlroos and Virtanen 1959; Hofman and Hofmanova 1969; Hofman and Hofmanova 1971) being released as aglycones by the activity of the enzyme β-glucosidase (Cambier et al. 1999; Baumeler et al. 2000). The main hydroxamic acid in maize is 2-O-β-d-glucopyranosyl-4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA-Glc) with lesser amounts of 2-O-β-d-glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc) and 2-O-β-d-glucopyranosyl-4-hydroxy-7,8-dimethoxy-(2H)-1,4-benzoxazin-3(4H)-one DIM2BOA-Glc) (Tipton et al. 1967). DIMBOA-Glc is also the major cyclic hydroxamic acid in wheat, whereas only DIBOA-Glc is found in rye (Virtanen and Hietala 1960).

These compounds have shown a wide spectrum of biological activities, (Honkanen and Virtanen 1960; Escobar et al. 1999; Schulz et al. 1994; Wolf et al. 1985) together with some of their degradation products (Bravo and Lazo 1996; Sahi et al. 1990), and synthetic analogues (Macías et al. 2005a). These properties have provoked high interest for these compounds and, consequently, a wide variety of methods for their isolation and synthesis.

Table 1. Compounds with (2H)-1,4-benzoxazin-3(4H)-one skeleton employed in this study.

• R1=OCH3; R2=R3= OH

2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

DIMBOA

• R1=H; R2=R3=OH

2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one

DIBOA

• R1=H; R2=O-b-D-glucopyranosyl; R3=OH

2-O-b-D-glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one

DIBOA-Glc

• R1=OCH3; R2=OH; R3=H

2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

HMBOA

• R1=H; R2=OH; R3=H

2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

HBOA

• R1=OCH3; R2=R3=H

7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

D-HMBOA

• R1=OCH3; R2=H; R3=OH

4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

D-DIMBOA

• R1=OCH3; R2=H; R3=OAc

4-acetoxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one

AMBOA

• R1=R2=R3=H

(2H)-1,4-benzoxazin-3(4H)-one

D-HBOA

• R1=R2=H; R3=OH

4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one

D-DIBOA

• R1=R2=H; R3=OAc

4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one

ABOA

Other metabolites related to 1,4-benzoxazin-3-ones have also attracted interest, such as 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)-ones, that were described by Niemeyer (1988). The most interesting compounds with this base structure are 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (HBOA) and 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (HMBOA). HBOA has been proposed as a biosynthetic precursor of benzoxazinones DIBOA and DIMBOA (Peng and Chilton, 1994; Kumar et al., 1994) and its analogue HMBOA has been detected in degradation experiments of DIMBOA carried out on wheat crop soils (Macías et al. 2004). Another point of interest is their degradation products (Table 2) that are produced in different systems, such as aqueous solutions (Macías et al. 2004; Woodward et al. 1978; Macías et al. 2005b), microbial biotransformation (Fomsgaard et al., 2004), or crop soils (Macías et al. 2004, Macías et al. 2005b; Gagliardo and Chilton 1992; Kumar et al. 1993). The first chemicals belonging to the DIBOA and DIMBOA degradation series are 2-benzoxazolinone (BOA) and 6-methoxy-2-benzoxazolinone (MBOA), respectively. The fact that these compounds are much more stable than their benzoxazinone precursors, and that they are commercially available, has facilitated many interesting works about their bioactivity (Honkanen and Virtanen 1960; Wolf et al. 1985; Bravo and Lazo 1996; Sahi et al. 1990; Macías et al. 2005a), and mode of action (Sánchez-Moreiras et al. 2004).

Table 2. Degradation compounds of benzoxazinones evaluated.

Benzoxazolinones

Aminophenoxazines

Malonamic acids

Miscellaneous

• R=H

Benzoxazolin-2(3H)-one

BOA

• R=OCH3

6-methoxybenzoxazolin-2(3H)-one

MBOA

• R1=H; R2=H

2-aminophenoxazin-3-one

APO

• R1=OCH3; R2=H

2-amino7-methoxyphenoxazin-3-one

AMPO

• R1=H; R2=OAc

2-acetamidophenoxazin-3-one

AAPO

• R1=OCH3; R2=OAc

2-acetamido-7-methoxyphenoxazin-3-one

AAMPO

• R=H

N-[2-hydroxyphenyl]malonamic acid

HPMA

• R=OCH3

N-[2-hydroxy-4 methoxyphenyl]

malonamic acid

HMPMA

2-aminophenol

APH

Another interesting group of degradation products is the aminophenoxazines (Table 2). The decomposition of benzoxazolinones seems to proceed via the corresponding 2-aminophenols, then further dimerization generating these tricyclic structures (Macías et al. 2004, Macías et al. 2005b; Gagliardo and Chilton 1992; Kumar et al. 1993).

Some endoparasitic fungi associated with DIBOA and DIMBOA producer plants (Zikmundova et al. 2002; Friebe et al. 1996; Friebe et al. 1998) have been shown to produce the malonamic acids N-[2-hydroxyphenyl]malonamic acid (HPMA) and N-[2-hydroxy-4-methoxyphenyl]malonamic acid (HMPMA) as detoxification metabolites. Their phytotoxicity profiles have been recently reported, confirming their detoxification role (Macías et al. 2005a).

With these antecedents, we prepared a collection of compounds including the four skeletons described (1,4-benzoxazin, benzoxazolinones, aminophenoxazines and malonamic acids) and the following structural variations: presence or absence of methoxyl group on the benzene ring; presence or absence of hydroxyl group at C-2 position, hydroxamic acid or lactam moiety; acetylation at different positions and demethylation. The obtained compounds were bioassayed on eight plant species including standard target species [Triticum aestivum L. (wheat), Allium cepa L. (onion), Lepidium sativum L. (cress), Lycopersicon esculentum Will. (tomato), and Lactuca sativa L. (lettuce)] and common weeds [Avena fatua L. (wild oat), Lolium rigidum Gaud. (rigid ryegrass), and Echinochloa crus-galli L. (barnyardgrass)] in order to make a comparative study of the structural requirement needed for the phytotoxic activity.

Preparation of benzoxazinoids and related compounds

Natural benzohydroxamic acids

DIMBOA and DIBOA (Table 1) have been obtained from natural sources by means of previously reported isolation procedures (Larsen and Christensen 2000; Barnes and Putnam 1987) from maize and rye, respectively. The DIBOA natural glycoside (2-O-β-d-glucopyranosyl-2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc, Table 1) was isolated from rye.

1,4-Benzoxazin-3-ones

For the synthesis of D-DIBOA, D-DIMBOA, ABOA and AMBOA (Table 1), the methodology described by Atkinson and collaborators (Atkinson et al. 1991) was employed (Scheme I). We have introduced some modification, as the use of DMF as solvent instead of THF in step (a), in order to increase the alkoxide solubility, and the modification of the sodium borohydride proportion (step b) to obtain the hydroxamic acid moiety preferentially to the lactam. These procedures were employed for DIMBOA analogues replacing the starting material 2-nitrophenol by 5-methoxy-2-nitrophenol.

Scheme I. Summary of reactions and conditions: a) KOH, EtOH, BrCH2COOEt, DMF, rt.; b) 1.2 mol eqs. NaBH4, Pd/C, H2O/dioxane (1:1), 0 ºC; c) 2.4 mol eqs. NaBH4, Pd/C, H2O/dioxane (1:1), rt.; d) Ac2O, Py, rt.; e) Toluene, reflux.; f) (MeO)2Mg, MeOH, rt.; g) TBDMSCl, Py, rt.; h) 1 atm H2, Pd/C, Ethyl acetate, rt.; i) Ethyl 3-chloro-3-oxopropionate, toluene, rt.; j) KOH, MeOH, H2O, 60 ºC.

HBOA (Table 1) was prepared via an acyl [3.3] sigmatropic rearrangement (Scheme I, step e) from ABOA, which allowed the functionalization at C-2 position. This reaction was previously described by Hashimoto (Hashimoto et al. 1983). We have changed benzene for toluene as solvent, which allowed higher reflux temperature. In these conditions, the reaction yield and selectivity increased from the original 30% to 70%. This sigmatropic rearrangement was not successful for the preparation of HMBOA (Table 1). Thus, a hemisynthesis from natural DIMBOA was optimized with just one reaction step (Scheme 2). The N-OH moiety of natural DIMBOA was reduced to N-H by employing samarium diiodide, a reagent described for selective reduction of oximes, hydroxylamines and hydroxamic acids (Keck et al. 1999), which has never been employed in this kind of compound.

Scheme II. Hemisynthesis of lactam HMBOA.

Hydroxyphenylmalonamic acids (III)

For the preparation of N-[2-hydroxyphenyl] malonamic acid (HPMA) (Table 2) and N-[2-hydroxy-7-methoxyphenyl]malonamic acid (HMPMA, Table 2), we adapted a previously reported procedure (Friebe et al. 1998) (Scheme I, steps from g to j). This reported method leads directly to both compounds, but we modified it by controlling protection and deprotection of both phenolic and amine moiety so that we could access modified 2-aminophenol with selectivity. This procedure avoided aminophenol dimerization, which would lead to aminophenoxazines. Thus, we got access to tert-butyldimethylsilyloxyanilines (both 5-methoxy and 5-H), and after catalytic hydrogenation, amidation and basic hydrolysis, both malonamic acids were obtained in high yield (68 %).

Aminophenoxazin-3-ones

APO and AAPO (Table 2) have been synthesized in large scale by using procedures previously reported (Gagliardo and Chilton 1992).

AMPO and AAMPO (Table 2) could not be obtained in the same way. We developed a new procedure (Scheme III) by reductive dimerization of 5-methoxy-2-nitrophenol (step a). 70 % yield of the dimer 2-amino-7-methoxyphenoxazin-3-one (AMPO) was obtained and further amine acylation (step b) yielded 2-acetamido-7-methoxyphenoxazin-3-one (AAMPO).

Scheme III. Summary of reactions and conditions: a) 1.2 mol eqs. NaBH4, Pd/C, H2O/dioxane (1:1), rt. b) AcOH, Ac2O, rt.

Additional compounds were evaluated in order to characterize their bioactivity and to explore the phytotoxicity of DIBOA degradation route chemicals. 2-Aminophenol (purchased from Sigma-Aldrich, Table 2) was evaluated, while benzoxazolinones BOA and MBOA were also purchased (Fluka Chemika and Lancaster Synthesis, respectively), and used as received.

The bioassay methodology has been optimized by us in the last years, from the point of view of statistical significance and a representative selection of target species. The species used were the standard target species: Triticum aestivum L. (wheat), Allium cepa L. (onion), Lepidium sativum L. (cress), Lycopersicon esculentum Will. (tomato), and Lactuca sativa L. (lettuce), as well as the common weeds: Avena fatua L. (wild oat), Lolium rigidum Gaud. (rigid ryegrass), and Echinochloa crus-galli L. (barnyardgrass) (Macias et al. 2000). The presence of wheat among the assayed species is especially interesting, since it helps to evaluate possible autotoxicity phenomena due to these compounds which are produced by wheat and related crops. Wild oat and rigid ryegrass are common weeds affecting Poaceae crops like wheat or barley. The results of these bioassays provided interesting information about the potential utilization of these natural products or analogues of them in real agronomic problems in which these weeds and crops are involved.

Structure-activity relationships

General bioactivity profiles

The most affected parameter was root length for all the active compounds, followed by shoot length. Effects of the assayed compounds (as IC50 for root lengths) are summarized in Table 3. Natural lactams (HBOA and HMBOA), and malonamic acids (HPMA and HMPMA) are excluded due to their lack of phytotoxic effect.

Natural allelochemicals and their synthetic analogues D-DIBOA, D-DIMBOA, and ABOA, were the most active compound groups. The rest of the analysed chemicals, which are present in natural benzoxazinone degradation routes, had moderate or null activity, except APO, which showed the highest inhibitory effects of the degradation products. The presence of wheat in the bioassay is especially valuable since this would allow for discovering any autotoxicity phenomenon associated with these wheat allelochemicals in the management of wheat and analogous crops. Moreover, wheat, together with lettuce, was the less affected species, as can be observed in Table 3. D-DIBOA and D-DIMBOA (Table 1) are the best compounds to illustrate this selectivity. We can point out the effects on wheat in comparison to those observed on the common wheat weeds A. fatua and L. rigidum.

Table 3. IC50 values (root length) for selected allelochemicals, synthetic analogues and degradation compounds.*

 

Lepidium sativum

Lactuca sativa

Lycopersicon esculentum

Triticum aestivum

Allium cepa

Lolium rigidum

Avena fatua

Echinochloa
crus-galli

LOGRAN©

>1

0.1-0.5

0.01-0.05

0.95

<0.01

0.05

0.24

0.61

DIBOA-Glc

-

>1

0.1-0.5

>1

0.15

0.27

0.27

0.5-1

DIBOA

0.1-0.5

0.1-0.5

0.1-0.5

>1

0.40

0.1-0.5

0.27

0.1-0.5

DIMBOA

0.24

0.1-0.5

0.15

>1

0.1-0.5

0.48

0.1-0.5

>1

D-DIBOA

0.05-0.1

0.86

0.61

0.89

0.05-0.1

0.47

0.19

0.33

D-DIMBOA

0.15

>1

0.21

0.94

0.21

0.1-0.5

0.15

0.71

D-HBOA

0.1-0.5

-

0.53

>1

0.1-0.5

0.60

0.74

0.81

D-HMBOA

0.97

>1

>1

>1

0.5-1

>1

0.97

>1

BOA

>1

2.0

0.59

-

0.9

0.72

0.92

-

MBOA

0.68

4.3

0.68

-

1.02

0.65

0.75

>1

APO

0.05

>1

0.13

0.71

0.08

0.01-0.05

0.01-0.05

0.5-1

AAPO

>1

>1

-

>1

>1

>1

>1

-

AMPO

-

-

-

-

>>1

>>1

>>1

>1

AAMPO

-

-

-

-

>>1

>>1

>>1

>>1

APH

0.42

0.27

>1

0.57

0.43

0.1-0.5

0.25

0.23

ABOA

0.01-0.05

0.50

0.41

0.66

0.04

0.33

0.21

0.71

*Values given in mM. When an IC50 value is given, the determination coefficient for the adjustment (r2; sigmoidal dose-response, constant slope) is higher than 0.90. When not given (failed correlation), concentration intervals containing the 50 % of inhibition are indicated. “-“: Inactive treatments (no significant activity value recorded).

This selective behaviour, specially observed for DIMBOA, DIBOA-Glc, and DIBOA, allows us to conclude that these natural allelochemicals, together with their degradation products, are not involved in intraspecific competition phenomena for wheat. Although these compounds and APO (Table 2) inhibited wheat growth, the concentrations assayed here are significantly higher than the natural ones, according to several estimations previously discussed by us (Macías et al. 2004). Their synthetic analogues (D-DIMBOA and D-DIBOA) did not affect wheat germination or growth, especially at the lowest concentrations, so the chemicals belonging to this series could be good candidates for the development of new herbicide models for wheat weeds control.

Structure-activity relationships

A SAR study was made on the basis of a cluster analysis (Figure 1) where effects on growth (root and shoot length) at all concentrations and on all assayed species for the compounds indicated was used to make the clustering.

According to their effects, the evaluated compounds can be divided in two groups: G1 for the most active ones, and G2 for moderate or null activities.

Group G1 includes the commercial herbicide Logran®, the aminophenoxazine APO and the modified benzoxazinone ABOA as the most active chemicals (G1A). The synthetic benzoxazinones D-DIBOA, D-DIMBOA, together with the natural products DIMBOA, DIBOA and DIBOA-Glc are placed, together with the degradation product 2-amino phenol in G1B group. G2 group is formed by degradation products and synthetic benzoxazinone lactams.

Regarding phytotoxicity requirements on the benzoxazinone skeleton, an increased toxicity can be observed when position C-2 is not oxidized, as in the case of ABOA, D-DIBOA, and D-DIMBOA. All these compounds are more active than the 2,4-dihydroxybenzoxazinones (natural allelochemicals DIMBOA and DIBOA). The role of the oxygen atom at N-4 is also crucial for the phytotoxic effect, since all 4-hydroxy benzoxazinones (DIBOA, DIMBOA, D-DIBOA, and D-DIMBOA) are more active than the corresponding lactams (HBOA, HMBOA, D-HBOA, and D-HMBOA).

Figure 1. Cluster analysis for selected allelochemicals, synthetic analogues and degradation products (root and shoot lengths).

The influence of the aromatic substitution is also determinant, since 7-methoxybenzoxazinones DIMBOA and D-DIMBOA have effects weaker than DIBOA and D-DIBOA, respectively, when joint influence on shoot and root lengths is considered. The fact that 4-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one (ABOA) was the most active benzoxazinone, indicates a possible direction in the further modification of these benzoxazinones in the search for higher phytotoxic effects. On the other hand, the 4-acetoxy derivative of D-DIMBOA (AMBOA), did not show any significant effect, so that the work on modification at N-4 seems to be effective just in benzoxazinones without a methoxy group at C-7.

The benzoxazinone degradation products examined have low or null phytotoxic activities. The transformation from benzoxazinone to benzoxazolinone skeleton, which is known to take place in a wide variety of systems and conditions, produces drastic phytotoxicity decay. The influence of the further degradations from benzoxazolinones depends on the presence or absence of a methoxy group on the aromatic ring. MBOA yields inactive chemicals such as AMPO and AAMPO. On the other hand, BOA yields 2-aminophenol (APH) and 2-aminophenoxazin-3-one (APO), which are the only active degradation chemicals, with phytotoxicity levels similar to or higher than benzoxazinones. APO is the only aminophenoxazine to show phytotoxicity, and the possible relation of this fact with the aqueous solubility/lipophillicity relationships for these chemicals has already been discussed (Macías et al, 2005a). It should be noted that the blocking of the 2-amino moiety directs to lower effects for methoxylated and non-methoxylated phenoxazines.

Conclusions

The phytotoxic effects shown by degradation products help to assign specific ecological roles for each one. In general, degradation of benzoxazinones is associated with detoxification. Regarding development of new herbicide models, 2-deoxy derivatives of natural benzoxazinones (D-DIMBOA and D-DIBOA) are the best leads for further modification in the search for phytotoxicity and selectivity. D-DIBOA, which includes in its structure all the optimal features for phytotoxicity enhancement (lack of hydroxy at C-2, presence of hydroxy at N-4, lack of methoxy group at the aromatic ring) is the best candidate, and some modifications, specially dealing with position N-4, can increase the effectiveness of these compounds, as results for the acetyl derivative ABOA show.

Acknowledgements

This work was financially supported by the program ‘Quality of life and management of living resources (1998 to 2002)’ of the European Union, FATEALLCHEM Contract No. QLRT-2000-01967, and the Ministry of Education and Science (MEC, Spain), Project No. CTQ2004-08314C02-01. Fellowships from Universidad de los Andes-Venezuela (A. O. B.), European Commission (European Union), and Junta de Andalucía-Spain (D. M.) are also gratefully acknowledged.

References

Atkinson J, Morand P, Arnason JT, Niemeyer HM and Bravo HR (1991). Analogs of the cyclic hydroxamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA): decomposition to benzoxazolinones and reaction with β-mercaptoethanol. Journal of Organic Chemistry 56, 1788-1800.

Barnes JP and Putnam AR (1987). Role of benzoxazinones in allelopathy by rye (Secale cereale L.). Journal of Chemical Ecology 13, 889-906.

Barnes JA, Putnam B, Burke BA and Aasen AJ (1987). Isolation and characterization of allelochemicals in rye herbage. Phytochemistry 26, 1385–1390.

Baumeler A, Hesse M and Werner C (2000). Benzoxazinoids-cyclic hydroxamic acids, lactams and their corresponding glucosides in the genus Aphelandra (Acanthaceae). Phytochemistry 53, 213–222.

Bravo R and Lazo W (1996). Antialgal and antifungal activity of natural hydroxamic acids and related compounds. Journal of Agricultural and Food Chemistry 44, 1569-1571.

Cambier V, Hance T, De Hoffmann E (1999). Non-injured maize contains several 1,4-benzoxazin-3-one related compounds but only as glucoconjugates. Phytochemical Analysis 10, 119-126.

Escobar CA, Sicker D and Niemeyer HM (1999). Evaluation of DIMBOA analogs as antifeedants and antibiotics towards the aphid Sitobion avenae in artificial diets. Journal of Chemical Ecology 25, 1543-1554.

Fomsgaard IS, Mortensen AG and Carlsen SCK (2004). Microbial transformation products of benzoxazolinone and benzoxazinone allelochemicals-a review. Chemosphere 54, 1025-1038.

Friebe A, Vilich V, Hennig L, Kluge M and Sicker D (1998). Detoxification of benzoxazolinone allelochemicals from wheat by Gaeumannomyces graminis var. tritici, G. graminis var. graminis, G. graminis var. avenae, and Fusarium culmorum. Applied and Environmental Microbiology 64, 2386-2391.

Friebe A, Wieland I and Schulz M (1996). Tolerance of Avena sativa to the allelochemical benzoxazolinone. Degradation of BOA by root colonizing bacteria. Angewandte Botanik 70, 150-154.

Gagliardo RW and Chilton WS (1992). Soil transformation of 2(3H)-benzoxazolone of rye into phytotoxic 2-amino-3H-phenoxazin-3-one. Journal of Chemical Ecology 18, 1683-1691.

Hashimoto Y, Ishizaki T, Seudo K and Okamoto T (1983). Rearrangement of 4-acetoxy-2H-1,4-benzoxazin-3(4H)-one. Chemical and Pharmaceutical Bulletin 31, 3891-3896.

Hofman J and Hofmanova O (1969). 1,4-Benzoxazine derivatives in plants. European Journal of Biochemistry 8, 109-112.

Hofman J and Hofmanova O (1971). 1,4-Benzoxazine derivatives in plants: absence of 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one from uninjured Zea mays plants. Phytochemistry 10, 1441-1444.

Honkanen E and Virtanen AI (1960). Synthesis of some 1,4-benzoxazine derivatives and their antimicrobial activity. Acta Chemica Scandinavica 14, 1214-1217.

Keck GE, Wager TT and McHardy SF (1999). Reductive cleavage of N-O bonds in hydroxylamines and hydroxamic acid derivatives using samarium diiodide. Tetrahedron 55, 11755-11772.

Kumar P, Gagliardo RW and Chilton WS (1993). Soil transformation of wheat and corn metabolites MBOA and DIM2BOA into aminophenoxazinones. Journal of Chemical Ecology 19, 2453-2461.

Kumar P, Moreland DE and Chilton WS (1994). 2H-1,4-Benzoxazin-3(4H)-one, an intermediate in the biosynthesis of cyclic hydroxamic acids in maize. Phytochemistry 36, 893-898.

Larsen E and Christensen LP (2000). Simple method for large scale isolation of the cyclic arylhydroxamic acid DIMBOA from maize (Zea mays L.). Journal of Agricultural and Food Chemistry 48, 2556-2558.

Macías FA, Castellano D and Molinillo JMG (2000). Search for a standard phytotoxic bioassay for allelochemicals. Selection of standard target species. Journal of Agricultural and Food Chemistry 48, 2512-2521.

Macías FA, Oliveros-Bastidas A, Marín D, Castellano D, Simonet AM and Molinillo JMG (2004). Degradation studies on benzoxazinoids. Soil degradation dynamics of 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and its degradation products, phytotoxic allelochemicals from Gramineae. Journal of Agricultural and Food Chemistry 52, 6402-6413.

Macías FA, Marín D, Oliveros-Bastidas A, Castellano D, Simonet AM and Molinillo JMG (2005a). Structure-activity Relationships (SAR) studies of benzoxazinones, their degradation products and analogues. Phytotoxicity on Standard Target Species (STS). Journal of Agricultural and Food Chemistry 53, 538-548.

Macías FA, Oliveros-Bastidas A, Marín D, Castellano D, Simonet AM and Molinillo JMG (2005b). Degradation Studies on Benzoxazinoids. Soil Degradation Dynamics of (2R)-2-O-β -D-Glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc) and Its Degradation Products, Phytotoxic Allelochemicals from Gramineae. Journal of Agricultural and Food Chemistry 53, 554-561.

Niemeyer HM (1988). Hydroxamic acids (4-hydroxy-1,4-benzoxazin-3-ones), defence chemicals in the Gramineae. Phytochemistry 27, 3349-3358.

Niemeyer HM, Pesel E, Copaja S, Bravo H, Franke S and Francke W (1990). Changes in hydroxamic acid levels of wheat plants induced by aphid feeding. Phytochemistry 28, 447–449.

Peng S and Chilton WS (1994). Biosynthesis of DIMBOA in maize using deuterium oxide as a tracer. Phytochemistry 37, 167-171.

Pratt K, Kumar P and Chilton W (1995). Cyclic hydroxamic acids in dicotyledonous plants. Biochemical Systematics and Ecology 23, 781-785.

Sahi SV, Chilton M and Chilton WS (1990). Corn metabolites affect growth and virulence of Agrobacterium tumefaciens. Proceedings of the National Academy of Sciences of the United States of America 87, 3879-3883.

Sánchez-Moreiras AM, Coba de la Peña T, Martínez A, González L, Pellisier F and Reigosa MJ (2004). In ‘Allelopathy’ Eds. FA Macías, JCG Galindo, JMG Molinillo and HG Cutler) pp 239-252. (CRC Press LLC, Boca Raton, Florida).

Schulz M, Friebe A, Kueck P, Seipel M and Schnabl H (1994). Allelopathic effects of living quack grass (Agropyron repens L.). Identification of inhibitory allelochemicals exuded from rhizome borne roots. Angewandte Botanik 68, 195-200.

Tipton CL, Klun JA, Husted RR and Pierson MD (1967). Cyclic hydroxamic acids and related compounds from maize. Isolation and characterization. Biochemistry 6, 2866-2870.

Virtanen AI and Hietala PK (1960). Precursors of benzoxazolinone in rye plants. Acta Chemica Scandinavica 14, 499-501.

Wahlroos Ö and Virtanen I (1959). The precursors of 6-methoxy-benzoxazolinone in maize and wheat plants, their isolation and some of their properties. Acta Chemica Scandinavica 13, 1906-1908.

Wolf RB, Spencer GF and Plattner RD (1985). Benzoxazolinone, 2,4-dihydroxy-1,4-benzoxazin-3-one, and its glucoside from Acanthus mollis seeds inhibit velvetleaf germination and growth. Journal of Natural Products 48, 59-63.

Woodward MD, Corcuera LJ, Helgeson JP and Upper CD (1978). Decomposition of 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one in aqueous solutions. Plant Physiology 61, 796-802.

Wu HW, Haig T, Pratley J, Lemerle D and An M (2001). Allelochemicals in wheat (Triticum aestivum L.): production and exudation of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one. Journal of Chemical Ecology 27, 1691–1700.

Zikmundova M, Drandarov K, Bigler L, Hesse M and Werner C (2002). Biotransformation of 2-benzoxazolinone and 2-hydroxy-1,4-benzoxazin-3-one by endophytic fungi isolated from Aphelandra tetragona. Applied and Environmental Microbiology 68, 4863-4870.

Zuñiga G and Massardo F. (1991) Hydroxamic acid content in undifferentiated and differentiated tissues of wheat. Phytochemistry 30, 3281–3283.

Previous PageTop Of PageNext Page