Natural products-based herbicides

Natural products represent an immense reservoir of new molecules for the development of pesticide agents. In particular, natural products based herbicides have become attractive in recent years for a few reasons. One of the reasons is that they are environmentally benign. Furthermore, the novelty of their structures offers the possibility of finding compounds with new mode of actions, thus diminishing the induction of plant resistance, a problem associated with commonly used synthetic herbicides. 

Thus, a synthetic source of promising allelochemicals is essential if we are to comprehensively study the agent s mode of activity and establish its basic structure-activity profile. The proposed work addresses this need. We will synthesize alleopathic natural products isolated from the sunflower (the heliannuols), and structurally related compounds, in optically pure form based on biomimetic phenol-epoxide cyclizations. The bioactivity of the targets and intermediates will be evaluated through laboratory tests on plant germination and growth. Bioassays will be performed on the synthetic intermediates to allow for the development of a preliminary structure-activity profile for these novel natural herbicides. 

Many new sugar based products present the advantage of being non-toxic and biodegradable. The products resulting from the telomerization of 1 with appropriate nucleophiles such as alcohols, amines, water, or carbon dioxide serve generally as useful intermediates in the synthesis of various natural products and fine chemicals [60-63], as precursors for plasticizer alcohols [56, 64], components of diesel fuels [65], surfactants [11, 66], corrosions inhibitors, and non-volatile herbicides [67]. 

NMR metabolomics has also been applied to investigate potential MOA. Plant researchers from BASF generated more than 400 1H NMR spectra from plants treated with different herbicides. Statistical analysis of the NMR spectra accurately clustered the extracts based on the metabolic action of the herbicides.41 NMR metabolomics may therefore offer the natural product researcher new ways to investigate MOA for compounds where activity is demonstrated but MOA is undetermined. 

Some 5 -0-(a-aminoacyl) derivatives of ribavirin have been made using DCC coupling.3l2 The 5 -0-sulfamoylribose derivative 229 was used in modified Vorbriiggen couplings with various bases to make a range of S -O-sulfamoyl nucleosides related to the herbicidal natural product lead compound, 2-chloroadenosine S -sulphamate, but most of the analogues were toxic in a mammalian cell line.313... 

Several of the top 20 pharmaceuticals in gross sales in 1992 were natural products or close derivatives thereof (eg. Mevacor, Ceclor). Of the top 20 crop chemicals in this same period, only one class of compounds, the pyrethroids, are based on a natural substance, the plant metabolite pyrethrin. Three active areas of chemistry have the potential to impact this situation within the next ten years the methoxyacrylate family of fungicides based upon the fungal metabolite, strobilurin Basta, a post-emergent broad-spectrum herbicide based upon the Streptomyces viridochromogenes metabolite phosphinothricylalanylalanine and avermectin, and its semi-synthetic derivatives, insecticides originating from Streptomyces avermitilis. 

Pyridine is a polar, stable, relatively unreactive liquid (bp 115°C) with a characteristic strong penetrating odor that is unpleasant to most people. It is miscible with both water and organic solvents. Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Pyridine can also be formed from the breakdown of many natural materials in the environment. 

Isophorone is a solvent for a large number of natural and synthetic polymers, resins, waxes, fats, and oils. Specifically, it is used as a solvent for concentrated vinyl chloride/acetate-based coating systems for metal cans, other metal paints, nitrocellulose finishes, printing inks for plastics, some herbicide and pesticide formulations, and adhesives for plastics, poly(vinyl) chloride and polystyrene materials (Papa and Sherman 1981). Isophorone also is an intermediate in the synthesis of 3, 5-xylenol, 3, 3, 5-trimethylcyclohexanol (Papa and Sherman 1981), and plant growth retardants (Haruta et al. 1974). Of the total production, 45-65% is used in vinyl coatings and inks, 15-25% in agricultural formulations, 15-30% in miscellaneous uses and exports, and 10% as a chemical intermediate (CMA 1981). 

Xenoestrogens, exhibiting a wide molecular diversity, are found in a number of cosmetic products, such as plasticizers, perfume fixatives, and solvents (e.g., dibutyl phthalate), industrial chemicals and pollutants such as insecticides (e.g., methoxychlor, DDT, and DDE), epoxy resins, and polycarbonate (e.g., bisphenol A), and herbicides (e.g., simazine). This group of chemicals has been classified as environmental endocrine disruptor compounds (EDCs), defined as exogenous agents that interfere with the synthesis, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development, and/or behavior. A list of representative chemicals is shown in Table 1 based on commercial usage. 

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