Oxone derivative

Phosphorothioates and phosphonothioates are of particular significance as insecticides. Schematically, it can be stated that these xenobiotics undergo activation by oxidative desulfuration, and detoxification by hydrolytic cleavage. Oxidative desulfuration transforms phosphorothioates and phosphonothioates to the corresponding oxon derivatives (see Chapt. 7 in [59]), which are highly toxic as potent inactivators of acetylcholinesterase [69]. This route of toxification can be competitive with and/or followed by cleavage reactions, which can be either hydrolytic or oxidative. 

In the case of activation reactions, such as the activation of the insecticide azin-phosmethyl to its potent anticholinesterase oxon derivative, a decrease in toxicity is apparent when rats are pretreated with the P450 inhibitor SKF-525A. 

Parathion and other phosphorothionates must be bioactivated to the oxon derivatives in order to be toxic. This is mainly done by the CYP enzymes... 

Cultures exposed at mo developmental stages for 10 days daily-in serum-free medium to chJorpyrifos, parathion, or their oxon derivatives (1 pJVf) on culture days 5-15 (immature) or 25-35 of culture (differentiated). Cells harvested immediately or after 11-day recovery. Activities of AChE, choline acetyl transferase (ChAT), glutamic acid dehydrogenase (GAD), glutamine synthetase, and CMP measured. OP effects on AChE activity compared to physostigminc. 

IC50 Values for Oxidized OP Compounds Table IV shows IC50 values and paraoxon equivalence values for selected phosphorothioate OP insecticides that were assayed with and without prior bromine oxidation. In addition, where commercially available, the oxon derivatives are also compared. The bromine oxidation protocol significantly increased the sensitivity of this assay to many of these insecticides. In about half of the cases the IC50 values were decreased between 20 and 300 times, however, several of the compounds showed only... 

These results show that differences in the inhibitory behavior for phosphorothioate insecticides and their oxon derivatives vary over a broad range. More specifically, the IC50 for malathion and its oxidative transformation product differ by almost 5000 times, whereas in the case of dimethoate, there is only a 20 fold increase in sensitivity between the parent compound and oxon derivative. Consequently, these results indicate that the efficiency of the oxidation was not the sole factor influencing the magnitude of the observed increase in sensitivity for the bromine oxidation step. The kinetics and products of bromine oxidation of phosphorothioate insecticides warrants further evaluation. 

Treatment of ethyl 10-methylthio-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxylate with oxone in aqueous MeOH at 0°C afforded 10-methylsulfonyl derivative (99H(51)1563). Methylthio group in a 7-(4-methylthiophenyl)-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- 7e]-l,4-benzoxazine-3-carboxamide was oxidized to a sulfoxide and a sulfone group (OOMIPl). 

Epoxidation of cyclooctene and other alkenes with Oxone (KHSO5) was promoted effectively in an aqueous micellar solution of an amphiphilic ketone (3.3).52 The amphiphilic ketone can be easily derived from hepta(ethylene glycol) monodecyl ether. 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

The epoxidation of nonfunctionalized alkenes may also be effected by chiral dioxiranes. These species, formed in situ using the appropriate ketone and potassium caroate (Oxone), can be formed from C-2 symmetric chiral ketones (29)[93], functionalized carbohydrates (30)[94] or alkaloid derivatives (31)[95]. One example from the laboratories of Shi and co-workers is given in Scheme 19. 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

Epoxidation using a chiral fructose-derived ketone is easy to carry out, as it occurs in aqueous conditions. The reactions were performed without any modification of the published procedure. The glassware has to be free of trace metal, which can decompose the oxone the use of a plastic spatula is recommended and the volumes must be measured using glass-graduated cylinders. Table 6.2 gives different examples of epoxides which can be obtained using the method prescribed. 

Oxidation of 2,3-epoxynorbomane to diol, ketohydroxy, and diketone derivatives was studied with RuCyaq. oxidant/CCl -CHjCN (co-oxidant=(I04) , H O, Oxone , (CIO)", (S Og) " (BrO )" was ineffectual) [73]. The system RuClj/aq. Na(10 )/CCl4-CH3CN oxidised substituted epoxides containing bicyclic [2.2.1] heptane skeletons, e.g. exo-2,3-epoxynorbomanes to the corresponding diketo compounds [74]. Stoicheiometric RuOyCCl converted 20,21-dihydroxy-lip,... 

Previously, some fluorocyclohexanones were used in a catalytic amount with Oxone for asymmetric epoxidation reaction, but they gave a poor ee . It was found later that chiral ketones derived from fructose work well as asymmetric epoxidation catalysts and show high enantioselectivity in reactions of /rani-disubstituted and trisubsti-tuted olefins ". Cis and terminal olefins show low ee under these reaction conditions. Interestingly, the catalytic efficiency was enhanced dramatically upon raising the pH. Another asymmetric epoxidation was also reported using Oxone with keto bile acids. ... 

Wozniak and Stec reported for the first time the application of Oxone for chemoselective and stereospecific oxidations of various P(III), phosphothio and phosphoseleno derivatives (equation 59) . ... 

A new method for conversion of oximes to the corresponding em-halonitro derivatives using NaCl or KBr with Oxone and wet basic alumina was reported (equation 64) °. When the reaction was carried out under the same conditions but by using wet neutral alumina, complex mixtures of compounds in which the parent ketone is the most abundant product (>50%), due to the oxidative deprotection of the oxime, was obtained. 

We recently reported our results on the asymmetric epoxidation of trans-disubstituted and trisubstituted alkenes, using Oxone as oxidant, catalyzed by readily available arabinose-derived 4-uloses containing tunable steric blockers that control the enantioselectivity of the epoxidation.Ulose (3), containing a 2, 3 -diisobutyl acetal unit, was the most efficient catalyst and displayed good enantioselectivity. 

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