Epoxide, hydration

The epoxide hydration in the nanoreactor is not only an energy-saving but also an environmentally benign process, which holds great potential for industry. It 

Epoxide rings of alkene and arene compounds are hydrated by enzymes known as epoxide hydrolases, the animal enzyme forming the corresponding trans-diols, although bacterial hydrolases are known that form d.v-diols. Although, in general, the hydration 

---

Photodegradation. Casida s group (15, 20) has studied the photodecomposition of R-20458 on silica gel and in water. The major aqueous photoproducts are summarized in Figure 1. The predominant photoproduct in aqueous solution resulted from epoxide hydration to the corresponding diol. The photoproducts on silica were quite similar to aqueous products with an enhanced yield of diepoxide and diminished yield of diol. Photosensitizer dyes had little effect on R-20458 photodegradation. 

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

Both rats and mice exhibited saturation kinetics when exposed to concentrations above 300 ppm [840 mg/m ]. The maximal rate of metabolism in vivo, which occurs via monoepoxides and diepoxide and subsequent epoxide hydration, is more than three times greater in mice than in rats. In-vitro studies and a physiological toxicokinetic model suggest that the rates of metabolism in humans is lower. 

Acid-catalysed sugar epoxide hydration has also been carrier) out in a few instances. Midler1207 1S0S and more recently Buchanan, ... 

Generally epoxide hydrations cited here will be of two types. The first involves heating the epoxide with water alone at 100-125°. frequently in a sealed tube The second, treating it with water at moderate temperaturew in the presence of a trace of acid. Meet commonly employed for this purpose is sulfuric acid although perchloric acid has likewise keen reported oil occasion Acetic acid, formic acid, hydrochloric add, hydrobromjc acid, and hydroiodio arid can be used... 

Several aryl-substituted ethylene oxides may be cited m connexion with epoxide hydration. For instance, a-methylstyreoe oxide Fives j. 2-dihydroxy-2-phenyl propano on careful treatment with cold dilute hydrochloric acid.4 9 The isomeric substance -methylstyrene oxide, which can exist in two geometric modifications, is reported to... 

Phase I reactions include microsomal monooxygenations, cytosolic and mitochondrial oxidations, co-oxidations in the prostaglandin synthetase reaction, reductions, hydrolyses, and epoxide hydration. All of these reactions, with the exception of reductions, introduce polar groups to the molecule that, in most cases, can be conjugated during phase II metabolism. The major phase I reactions are summarized in Table 7.1. 

The addition of H20 to epoxide rings, a process called epoxide hydration, is important in the metabolism of some xenobiotic materials. This reaction can occur, for example, with benzo(a)pyrene 7,8-epoxide, formed by the metabolic oxidation of benzo(a)pyrene, as shown in Figure 7.3. Hydration of an epoxide group on a ring leads to the trans dihydrodiols in which the -OH groups are on opposite sides of the ring. 

Epoxide rings of alkene and arene compounds are hydrated to form trans-diols. The enzymes that catalyze the addition of a molecule of water to an epoxide ring to yield diols are called epoxide hydrolases (also known as epoxide hydrases). Epoxide hydrolase activity has been detected in numerous species of insects. Enzymatic epoxide hydration of certain cyclodiene insecticides and their analogs has been demonstrated in the housefly, blowfly (Calliphora erythrocephala), yellow mealworm (Tenebrio molitor), Madagascar cockroach (Gromphadorhina portentosa), southern army worm (Spodoptera eridania), and red flour beetle (Tribolium castaneum). Epoxide hydrolase is also important in the metabolism of juvenile... 

Epoxidation by the introduction of an oxygen atom into flunarizine produced l-[bis(4-fluoro-phenyl)methyl] - 4 - [(3-phenyloxiran - 2 - yl)methyl] piperazine (metabolite 2) and epoxide hydration to a diol, 3-[4-[bis(4-fluorophenyl)methyl]-l-piper-azinyl]-l-phenyl-l,2-propanediol (metabolite 10). Lavrijsen et al. (1992) found metabolites formed by epoxidation at the double bond (metabolite 2) and epoxide hydration (metabolite 10) in incubates with subcellular hepatocyte fractions of male and female rats. Metabolites formed by epoxidation and epoxide hydration were not detected in vivo (Meuldermans et al. 1983), probably because the resulting metabolites were metabolised in vivo, much more quickly than in vitro, into secondary metabolites. A diol metabolite, however, was described for the metabolism of l-butyl-4-dimamyl-piperazine in guinea pigs (Morishita et al. 1978). With supernatant fractions a rapid disappearance of the epoxide intermediate from incubate was observed. This seems to indicate that, for the epoxide hydrolysis, besides microsomal epoxide hydrolase, cytosolic epoxide hydrolase might also be involved. 

Nucleophilic. In view of the ability of epoxides to become hydrated to the diol under aqueous alkaline conditions, the analogous addition of water to epoxides by enzymes will be considered in this section. The en mes responsible for epoxide hydration (epoxide hydrases) in animal liver systems have been purified, assayed using [7- H]styrene oxide,and tested for substrate and inhibitor -ass specificity. The current interest in these epoxide hydrases is mainly due to their close association with aryl monooxygenase enzymes and thus the total metabolism of olefinic and arene substrates via epoxides) in animals. The isolation of the antibacterial compounds aeroplysinin-1 (358) and aeroplysinin-2 (359) from the sponge Verongia aerophoba might be explained by the initial enzymatic formation of the unstable arene oxide (357), which can subsequently be hydrated by an epoxide hydrase enzyme, to form what the authors consider... 

In order to clarify the formation pathway of oxidation products 16 and 17 from citral (10 and 12), the effect of UV light, and AAPH, that is, radical initiator, under acidic or neutral conditions was studied (Table IV). The oxidation products 16 and 17 also increased using AAPH instead of UV light under acidic conditions. However, under neutral conditions, epoxides 40 and 41, the intermediates, were obtained instead of 16 and 17 (28-29). The epoxides 40 and 41 were converted into 16 and 17 by the furan-ring formation under acidic conditions. Therefore, as shown in Figure 7, there seemed to be the alternative pathway via epoxidation, hydration, and cyclization compared with Grein s report (4). 

Phase I reactions include oxidation, reduction, hydrolysis, epoxide hydration, and dehydrohalogenation reactions. The cytochrome P450 oxygenase system (CYP450) is the most important one in the metabolism of foreign chemicals. These enzymes that oxidize xenobiotics are widely distributed in the body. They are found in high... 

---