Insecticides analogues

The hazards of human poisoning by the parathions have stimulated the development of safer analogues. Two chlorinated derivatives have gready reduced mammalian toxicides. Dicapthon [2463-84-5], 0,0-dimethyl 0-(2-chloro-4-nitrophenyl) phosphorothioate (63) (mp 53°C), has rat LD qS of 400, 330 (oral) and 790, 1250 (dermal) mg/kg. Chlorthion [500-20-8], 0,0-dimethyl 0-(3-chloro-4-nitrophenyl) phosphorothioate (64) (mp 21°C, <71.437), has rat LD qS of 890, 980 (oral) and 4500, 4100 (dermal) mg/kg. These compounds have been used as household insecticides. 

Degraeve N, Moutschen J. 1984. Absence of genetic and cytogenetic effects in mice treated by the organophosphorus insecticide parathion, its methyl analogue, and paraoxon. Toxicology 32 177-183. 

Particularly the chlorinated compounds have enjoyed range of applications vinyl chloride (chloro-ethene) as monomer for the production of PVC, tetra- and trichloroethenes as solvents for degreasing, and the insecticides l,l,l-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and isomers of hexachlorocyclohexane (HCH) (benzene hexachloride). The biodegradation of fluorinated aliphatic compounds is generally different from the outlines that have emerged from investigations on their chlorinated, brominated, and even iodinated analogues. They are therefore treated separately in Part 4 of this chapter. 

The preparation of 3-vinylpyrroles was investigated utilizing the Horner-Wads worth-Emmons reaction with 3-formyl-lV-tosylpyrrole <06S1494>. The intramolecular acylation of pyrrole-2-Weinreb amides provided access to novel indolizinone derivatives <06T6182>. The amidation of pyrrole-2-carbonyl chloride was utilized as a key step in the preparation of pyrrole-oxazole analogue 90 of the insecticide Pirate <06S1975>. 

A parallel synthesis of novel pyrrole-oxazole analogues of the insecticide Pirate was performed through the dehydration of acylaminoketones with POCl3<06S1975>. 

Fenophos (O-ethyl-S-phenylethyl-phosphorodithioate) insecticide has been determined in soil by gas chromatography. Fenophos is known to degrade to its oxygen analogue (O-ethyl-S-phenylethyl phosphonothioate) in soil but none was found in the soil samples examined [93],... 

Organic phosphates, phosphonates, and analogues are of interest in medicinal chemistry as drugs or prodrugs, and in toxicology mainly as plasticizers, insecticides, or warfare agents. Their breakdown by enzymatic routes has received marked attention since many years, but it is most unfortunate for the advancement of science that an unknown number of highly relevant results remain classified information. 

Flupyrazofos (9.75) is an insecticide whose relatively simple metabolic scheme appears quite informative. Indeed, rat liver microsomes formed the oxon analogue as the only detectable primary metabolite [150], The latter then underwent chemical hydrolysis to the dephosphorylated phenol with a tm value of ca. 50 min at pH 7.4 and 37°. In rat liver microsomes, the phenol appeared to be produced exclusively from flupyrazofos oxon, indicating the resistance of flupyrazofos toward chemical hydrolysis. 

Another relevant example is that of the insecticide crufomate (9.83), which, in sheep, underwent various reactions of C-oxidation, as well as hydrolysis of the C-N bond to yield phosphate analogues as urinary metabolites [148a], These phosphates accounted for almost 15% of a dose in urine, indicating that the reaction of hydrolysis was a significant one in this case. 

Glotfelty, D.E., Majewski, M.S., and Seiber, J.N. Distribution of several organophosphorus insecticides and their oxygen analogues in a foggy atmosphere, Environ. Sci. Technol, 24(3) 353-357, 1990. 

Bi analogues. Also omitted are the phosphorothioic acid derivatives, such as the insecticide diazinon, and related compounds. Unnatural nucleoside derivatives have been given only brief mention, since the base, rather than the sugar, is our target in this review. 

Other activities were reported for sarcophins, e.g. potent cancer chemopre-ventive and insecticidal activity. Sarcophine and analogues were also synthesized for structure-activity studies so as to find compounds less toxic but with similar activities. 

The discovery in the early years of the 20 century that certain phosphate esters possess mammahan toxicity and insecticidal properties heightened interest in this class of compounds, both in agriculmre and as potential agents in chemical warfare. Parathion became the practical choice as a broad-spectrum insecticide because of its greater stability and lower mammalian toxicity compared to its P=0 analogue, paraoxon . 

Richardson s interest in these trehalose epoxides stemmed from his desire to prepare a wide range of modified trehalose analogues for evaluation as inhibitors of the trehalase of insects, as trehalose is known to be the storage carbohydrate of many insects and good inhibitors of this processing enzyme could potentially function as green insecticides. 

Unsaturated 5(4//)-oxazolones have also been used as intermediates to prepare analogues with diverse biological activities. For example, the oxazolone derived from 4-biphenylcarboxaldehyde is a synthetic precursor of the antiinflammatory agent 4-biphenylacetic acid." In addition, 2-substituted oxazolones derived from 2-thioarylbenzaldehydes are starting materials for the preparation of dibenzothie-pine derivatives that are useful to treat schizophrenia." Other oxazolones have been used as intermediates to prepare insecticides and acaricides." ... 

Glotfelty, D. E M. S. Majewski, and J. N. Seiber, Distribution of Several Organophosphorus Insecticides and Their Oxygen Analogues in a Foggy Atmosphere, Environ. Sci. Technol, 24, 353-357 (1990). 

A. Elbert, H. Overbeck, K. Iwaya and S. Tsuboi, Imidacloprid, a Novel Systemic Nitromethylene Analogue Insecticide for Crop Protection , in Brighton Crop Protection Conference - Pests and Diseases 1990 , British Crop Protection Council, Farnham, UK, 1990, Vol. 1, pp. 21-28. 

M. Elliott, Synthetic Insecticides Related to Natural Pyrethrins , in Crop Protection Agents from Nature natural products and analogues , ed. L.G. Copping, Royal Society of Chemistry, Cambridge, UK, 1996, pp. 254-300. 

Other important enzyme inhibitors of this type are the organophosphorus compounds. Thus, after metabolism to the oxygen analogues, the insecticides parathion and malathion (chap. 4, Fig. 25) (Fig. 5.12) form complexes with the enzyme acetylcholinesterase as described in more detail in chapter 7. 

Both compounds included here are experimental and in each case the pyridine is a benzene replacement and is not essential for the activity. The urea (103) (79SAP7802440) is a member of a highly active series that kill insects by disrupting the formation of new insect cuticle, through inhibition of chitin synthesis. The cyclopropane ester (104) (78GEP2810881) is a heterocyclic analogue of the pyrethroid insecticides, an extremely successful new class which are active on a wide range of insects. 

Preparation of a mimetic of the cyclic peptide jaspamide was reported in 1988. 87 Compound 41 (Scheme 17) was designed to mimic the type-II (1-turn of the peptide, which contained the proposed pharmacophoric phenol and 2-bromoindole functional groups. This analogue displayed interesting insecticidal activity against the tobacco budworm, Heliothis vireseins. 

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