Hexobarbital epoxide

In contrast, a number of alkene epoxides (10.3) are chemically quite stable, i.e., intrinsically less reactive than arene oxides. Examples of epoxide metabolites that have proven to be stable enough to be isolated in the absence of degrading enzymes include 1,2-epoxyoctane (10.4), 1,2-epoxycyclohex-ane (10.5), 1-phenyl-1,2-epoxy ethane (styrene oxide, 10.6), and cis- 1,2-diphenyl-1,2-epoxyethane (cfv-stilbene oxide, 10.7) [12], The same is true of alclofenac epoxide (10.8), hexobarbital epoxide (10.9), and a few other epoxides of bioactive compounds. 

The peculiar reactivity of epoxides of 5-vinylbarbiturates (10.65, Fig. 10.17) has been discussed in Sect. 10.5.3. Here, we note that hexobarbital epoxide (10.9) shows the same reactivity and decomposes via the same retro-aldol reaction to form 5-(l-methylbutyl)barbiturate [193]. 

Walter Reed-Wistar and Charles River male adult rats were exposed to oral doses of turpentine or to turpentine vapors, which consisted of a- and p-pinene. These exposures were followed by oral administration of heptachlor epoxide or of one of three pesticides, paraoxon, heptachlor, or parathion, or by an intraperitoneal injection of hexobarbital. The studies revealed that pretreatment with turpentine reduced hexobarbital sleeping time, reduced the parathion LDso, and increased the heptachlor LDso. The paraoxon and heptachlor epoxide LOo values were unchanged. a-Pinene and P-pinene vaporized from turpentine had no effect on either hexobarbital sleeping time or parathion, paraoxon, or heptachlor epoxide mortality but did increase the heptachlor LDso (Sperling et al. 1972). The authors speculated that increases in hepatic microsomal enzyme activity are responsible for these differences. 

The carcinogenicity of af la toxin is reduced by protein deficiency, presumably because of reduced metabolic activation to the epoxide intermediate, which may be the ultimate carcinogen, which binds to DNA (Fig. 5.14). A deficiency in dietary fatty acids also decreases the activity of the microsomal enzymes. Thus, ethylmorphine, hexobarbital, and aniline metabolism are decreased, possibly because lipid is required for cytochromes P-450. Thus, a deficiency of essential fatty acids leads to a decline in both cytochromes P-450 levels and activity in vivo. 

Simultaneous carbamazepine-10,11-epoxide, clonazepam, dihydrodihydroxycarbamaze-pine, hexobarbital, p-hydroxyphenobarbital, 5-(m-hydroxyphenyl)-5-phenylhydantoin, 5-(p-hydro QT)henyl)-5-phenylhydantoin, nitrazepam, phenobarbital, phenylethylmaleimide, phenytoin, primidone... 

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