S. A. Roslavtseva

Synthesis and physiological activity of new organophosphorus pesticides of 1,3,2-oxazaphosphorinane series

Methods for the synthesis of 2-aryloxy(arylthio)- and 2-alkoxy(alkylthio)-2-thio(oxo)-1,3,2-oxazaphosphorinanes and theirN-substituted derivatives based on the reactions of the corresponding dichlorophosphates, dichlorothio-, and dithiophosphates with 3-aminopropan-1-ol or its substituted derivatives in the presence of Et3N or aqueous alkali under phase transfer catalysis conditions, as well as by the reaction of the tetramethylammonium salt of 2-hydroxy-2-thio-1,3,2-oxazaphosphorinane with alkyl- and acyl halides, by that of 2-chloro-2-thio-1,3,2-oxazaphosphorinane with sodium thiolates, and by other methods, were developed. The compounds obtained exhibit high nematocide activity but low toxicity for mammals. Some active synergists for permethrine were found among these compounds.

Synthesis and biological activity of some 1,3,2-diheteraphosphorinanes and their acyclic analogs

Methods were developed for the synthesis of 2-butylthio-2-oxo-1,3,2-oxazaphosphorinane, 2-butylthio-2-thioxo-1,3,2-dioxaphosphorinane, and 2-butylthio-2-thioxo-1,3,2-diazaphosphorinane, as well as of acyclicS-butylO-ethyl (diethylamido)phosphorothioates and-dithioates andS-butyl bis(diethylamido)phosphorodithioate. These compounds can serve as models of possible metabolites of cyclic compounds. Based on the data obtained in studies of the antiesterase activity of the resulting compounds and their synergistic activity in mixtures with permethrine, a possible mechanism ofin vitro andin vivo biological action of diheteraphosphorinanes was proposed.

Synthesis and physiological activity of trialkyl phosphorothioates and trialkyl phosphorodithioates containing fragments of N-acylated amino acids

A series of S-[N-acyl-N-(alkoxycarbonylalkyl)aminomethyl] O,O-dialkyl phosphorothioates and -dithioates were prepared by the reactions of the corresponding alkali salts of dialkyl phosphorothioates or dialkyl phosphorodithioates with esters of N-acyl-N-(chloromethyl)glycine or N-acyl-N-(chloromethyl)-β-alanine and by the reactions of dialkylphosphorothioic or dialkylphosphorodithioic acids with N-acylated amino acids or their esters and paraformaldehyde in the presence of gaseous HCl. Some of the resulting compounds proved to be active permethrine synergists.

Synthesis, Biological Activity and Mechanism of Action of 1,3,2-Oxazaphosphorinane Derivatives

Abstract The title compounds were obtained by the reaction of the corresponding phosphorodichloridates with 3-aminopropanol-1 in the presence of an organic base or under phase transfer conditions, and by some other methods. They are highly active nematocides and sinergists to permethrin with low toxicity to mammals. Some peculiarities of mechanism of action of the compounds were established.

Synthesis of new organothiophosphorus insectoacaricides containingN-acylated amino acid fragments

Methods for the synthesis ofO-alkylS-(N-acyl-N-alkoxycarbonylalkyl)aminomethyl (methyl)thio- and -dithiophosphonates based on the reaction between alkaline-metal salts ofO-alkyl (methyl)thio- and -dithiophosphonates and N-alkoxycarbonyl-N-chloromethylglycine or -β-alanine esters and by treatment ofO-alkyl (methyl)dithiophosphonoates andN-acylated amino acids or their esters with paraform in the presence of HCl were developed. The compounds obtained exhibit high insectoacaricide activity and selectivity.

Interaction with Esterases and Mechanism of Synergistic Action of Thio- and Dithiophosphates Containing the Fragments N-Acylated Glycine and β-Alanine

We studied the interaction between O,O-diethyl-S-[(N-acyl-N-alkoxycarbonylalkyl)aminomethyl]thiophosphates and mammalian cholinesterases as well as esterases from insect tissue extracts by kinetic methods and disc electrophoresis. The coefficients of combined effect of these compounds or their dithioanalogs with permethrin were determined. The obtained data suggest that the synergistic effect on the common cockroaches and houseflies is chiefly due to carboxylesterase inhibition by monothioderivatives and monooxygenase suppression by dithioderivatives, respectively.

[Specific interaction between esterases and 2-butylthio-2-thio-1,3,2-oxazaphosphorynane and its cyclic and acyclic analogs].

We studied the anticholinesterase and anticarboxylesterase effects of 1,3,2-oxazaphosphorynane derivatives and certain cyclic and acyclic analogs on the two enzymes of homoiotherms (ACE from human erythrocytes and BuCE from horse serum) as well as the enzymes from insect tissues (the nerve cord of the American cockroach and the cephalic region of the domestic fly). The differences in in vitro antiesterase activity of cyclic thionic and the corresponding oxo derivatives of phosphorinane were revealed. The mechanism of the esterase active center phosphorylation not only splitting off the outgoing group (in vivo) but also opening the cycle by P–O bond (in vitro and possibly in vivo) is usually proposed to explain the higher inhibiting activity of the thionic compounds compared to the oxonic ones. The possible involvement of this phosphorylation mechanism in the synergistic activity of the studied compounds is discussed.

Some esters of phosphorus thioacids that contain the fragments of cyclic amino acid derivatives

ConclusionsThe reaction of the salts of phosphorus thio- and dithioacids with the 1,4-di(chloroacetyl)-and 1,4-di(chloromethyl)-2,5-diketopiperazines, and also with 1-chloromethyl-5-carbethoxy-2-pyrrolidinone, gave new thio- and dithiophosphorus compounds, which display either a moderate or weak insecticidal and acaricidal activity and a substantial toxicity for animals in a number of cases.

Synthesis, reaction with esterases, and toxicity of O-alkyl S-(carbalkoxymethylmercapto)methyl methylthiophosphonates

Conclusions1.A number of O-alkyl S-(carbalkoxymethylmercapto)methyl methylthiophosphonates was obtained by reacting the sodium salts of methylthiophosphonic acids with halo derivatives.2.It was found for the obtained compounds that increasing the size of the alkyl in the alkoxyl group on the phosphorus atom leads to an increase in the reaction rate with the esterases of warm-blooded animals and arthropoda, whereas the toxicity of the compounds decreases for the arthropoda.

Methyldithiophosphonates that contain mercaptoacetic acid moieties

Conclusions1.Some O-alkyl methyldithiophosphonates, containing mercaptoacetic acid moieties in the alkthiol radical, were synthesized by alkylating the salts of O-alkylmethyldithiophosphonic acids with halo derivatives.2.Some of the obtained compounds have a high insectoacaricidal activity, which approaches the activity of the standards Metaphos and Rogor.