Thiohydroximates

Glucosinolates derive from amino acids by conversion to an aldoxime, R-CH=N-OH. In a not well understood process, the aldoximine is converted to a thiohydroximic acid, R-C(SH)=N-OH the introduced sulfur is likely derived from... 

Sealants obtained by curing polysulfide liquid polymers with aryl bis(nitrile oxides) possess stmctural feature of thiohydroximic acid ester. These materials exhibit poor thermal stability when heated at 60°C they soften within days and liquefy in 3 weeks. Products obtained with excess nitrile oxide degrade faster than those produced with equimolar amounts of reagents. Spectroscopic studies demonstrate that, after an initial rapid addition between nitrile oxide and thiol, a second slower reaction occurs which consumes additional nitrile oxide. Thiohydroximic acid derivatives have been shown to react with nitrile oxides at ambient temperature to form 1,2,4-oxadiazole 4-oxides and alkyl thiol. In the case of a polysulfide sealant, the rupture of a C-S bond to form the thiol involves cleavage of the polymer backbone. Continuation of the process leads to degradation of the sealant. These observations have been supported by thermal analysis studies on the poly sulfide sealants and model polymers (511). 

In Ukraine during the 70-80-ies of the last century, a new direction appeared in the development of ChR on the basis of previously unknown thiohydroxime esters, which are close structurally to acetylcholine [13-15], When working out on this direction, diethyxime ... 

REED, D.W., DAVIN, L JAIN, J.C., DELUCA, V., NELSON, L., UNDERHILL, E.W., Purification and properties of UDP-glucose thiohydroximate glucosyltransferase from Brassica napus L. seedlings, Arch. Biochem. Biophys., 1993,305,526-532. 

GUO, L., POULTON, J.E., Partial purification and characterization of Arabidopsis thaliana UDPG Thiohydroximate glucosyltransferase, Phytochemistry, 1994, 36, 1133-1138. 

The oxime, 34, is glycosylated by a UDPG-thiohydroximate glucosyltransferase, and subsequently sulfonated by sulfotransferase to yield a glucosinolate of the type Thus, aldoximes generated by initial oxygenation of amino acids are found to serve as substrates of a wide variety of plant enzymes that act directly at the hydroximino function. 

FOO, H.L., GR0NNING, L.M., GOODENOUGH, L., BONES, A.M., DANIELSEN, B-E., WHITING, D.A., ROSSITER J.T., Purification and characterisation of epithiospecifer protein from Brassica napus Enzymic intramolecular sulphur addition within alkenyl thiohydroximates derived from alkenyl glucosinolates, FEBS Letts., 2000,468,243-246. 

It seems that this type of oximes may be referred to cholinesterase reactivators of the third generation. This group of compounds lacks the disadvantages inherent to reactivators of the 1st and 2nd generations. Thus, thiohydroxime esters are low toxic and stable in aqueous solutions. Being the substances having a tertiary nitrogen atom in their structure, they penetrate the hematoencephalic barrier and enter CNS readily. 

The cholinolytic properties of reactivator-cholinolytics were characterized in in vitro tests on the model of contracture suppression in rat s isolated intestine, induced by ACh. Antidotic-and-therapeutic effects of the compounds were studied in the model of rats intoxication with dichlorvos. Therefore, it was for the first time that the synthesis of ChR-cholinolytics, as new antidotes of OPC, was realized in the rank of thiohydroxime esters. 

The analysis of literature indicates that the search of antidotes for the treatment of OPC intoxications during the second half of twentieth century was performed preferably among H-oximes and thiohydroxime esters. A great number of active compounds were synthesized and studied (2-PAM, TMB-4, HI-6, HGG-12, HGG-42, HLo-7, alloxime, aphine, carboxime, di-ethyxime, etc ). However, oximes may be only considered as one of the basic components of formulas. The usage of any of them as monotherapy does not ensure a high antidotic effect. 

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