Isolation and Synthesis of Allelochemicals from Gramineae:  Benzoxazinones and Related Compounds

Abstract

Compounds with a (2H)-1,4-benzoxazin-3(4H)-one skeleton have attracted the attention of phytochemistry researchers since 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) were isolated from plants belonging to the Poaceae family. These compounds exhibit interesting biological properties, such as phytotoxic, antimicrobial, antifeedant, antifungal, and insecticidal properties. These chemicals, in addition to a wide variety of related compounds involved in their metabolism, detoxification mechanisms, and degradation on crop soils and other systems, have high interest and in some cases potential agronomic utility. This paper presents a complete review of the methods employed for their synthetic obtention in addition to some of the authors' own contributions to their chemistry. The degradation and phytotoxicity experiments carried out in ongoing research into the potential agronomic utility of these compounds required large amounts of them, which were obtained from natural sources. This paper presents a modified methodology to access DIMBOA from Zea mays cv. Apache and to obtain 2-O-beta-D-glucopyranosyl-2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc) and DIBOA from Secale cereale L. New synthetic methodologies were employed for the obtention of the lactams 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one and 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and the malonamic acids N-(2-hydroxyphenyl)malonamic acid and N-(2-hydroxy-7-methoxyphenyl)malonamic acid. The aminophenoxazines 2-amino-7-methoxyphenoxazin-3-one and 2-acetamido-7-methoxyphenoxazin-3-one have been synthesized in the authors' laboratory by novel procedures. All of the methodologies employed allowed the desired compounds to be obtained in high yield and in an easy-to-scale manner.

Study of the role played by NfsA, NfsB nitroreductase and NemA flavin reductase from Escherichia coli in the conversion of ethyl 2-(2′-nitrophenoxy)acetate to 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIBOA), a benzohydroxamic acid with interesting biological properties

“…4). These yields are close to the values obtained in the chemical process (77%) described in Macías et al (2006b).…”

“…pKD46 is an easily curable, low copy number plasmid containing the lambda phage Red recombinase under the control of an arabinose inducible promoter containing the Cre recombinase (Datsenko and Wanner 2000 Fig. 1 Benzohydroxamic acid synthesis: a first step: synthesis of ethyl 2-(2′-nitrophenoxy)acetate (precursor) (2) using 2-nitrophenol (1) as starting material described by Macías et al (2006b); b second step:…”

“…Recently, the chemical synthesis of an analogue of these compounds known as D-DIBOA [4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one] was simplified to only two steps (Macías et al 2001(Macías et al , 2006b. The product of the first step is the ethyl 2-(2′-nitrophenoxy)acetate (Macías et al 2006b) (Fig.…”

“…The product of the first step is the ethyl 2-(2′-nitrophenoxy)acetate (Macías et al 2006b) (Fig. 1a), which is henceforth referred to as the precursor (Valle et al 2011).…”

“…The second step involves the reduction of the nitro group followed by a cyclisation (Fig 1b). This second step, which occurs in complex conditions, requires the usage of an expensive catalyst and renders undesired products (Macías et al 2006b). In a previous work, we demonstrated that this second step could be carried out by Escherichia coli JM109 (Fig.…”