Cyclopropanone, hydration

Thus the cyclopropanone hydrate 21 is an inhibitor of yeast aldehyde dehydrogenase (ALDH) through the nucleophilic substitution of a hydroxyl group by an enzymic thiol 47 leading to the cyclopropanone hemithioacetal 24 a, Eq. (16) [211. 

Horse radish peroxidase on the other hand, is a hemoprotein which is inhibited by alkylation of the porphyrin ring 48 by a -propionic acid radical resulting from the ring cleavage of the cyclopropanone hydrate 21, providing the car-boxylate 49,Eq. (17). 

The polymerization of cyclopropanone is initiated °) by traces of water and is inhibited 15> by moisture scavengers such as acetyl chloride. The terminal groups are apparently hemiketal units since a,co-diacetoxy-poly(oxycyclopropylidenes) 85 are isolated from a mixture of cyclopropanone hydrate, diazomethane and excess ketene. 80>... 

The free radical products generated by peroxidases are highly reactive species that can, in some instances, covalently modify the heme group of the enzyme (Fig. 5.10). In the case of HRP, the substrates for which this type of reaction has been observed include aryl and alkyl hydrazines [55, 56], the azide anion [57], nitromethane [58], cyclopropanone hydrate [59], and alkyl acids [60]. Free radicals... 

Wiseman JS, Nichols JS, Kolpak MX (1982) Mechanism of inhibition of horseradish peroxidase by cyclopropanone hydrate. J Biol Chem 257 6328-6332... 

Coprine (29) is an unusual y-glutamylamide of cyclopropanone hydrate (158). The substituted hemiaminal (29) is stable in aqueous solutions but can be cleaved by hydrolytic... 

Coprine, isolated from the Coprinus atramentarius mushroom, and identified as hydroxycyclopropyO-L-glutamine ", 135, is the first example of a natural product containing a cyclopropanone equivalent. Coprine inhibits mouse liver aldehyde dehydrogenase in vivo but not in vitro Cyclopropanone hydrate (170), which can be derived from coprine by hydrolysis to 169 (equation 39), inhibits the enzyme both in vivo and in vitro. Cyclopropanone hydrate has thus been proposed as a metabolite of coprine which is the active agent causing the toxic effects ... 

Cyclopropanone hydrate has been reported to be a potent but reversible inhibitor of a number of enzymes which are sensitive to thiol reagents The kinetics of inhibition... 

Cyclopropanone hydrate forms a stable thiohemiketal with the active-site thiol which is not oxidized by nicotinamide adenine dinucleotide (NAD). This hydrate has also been found to be a suicide inhibitor for horseradish peroxidase flavoenzyme alcohol oxidase and quinoprotein alcohol dehydrogenases ... 

Poisoning with mushrooms in this group occurs when ethanol is consumed shortly before or within 5 days after eating the mushrooms. Coprine (N(5)-(l-hydroxy cyclopropyl)-L-glutamine) is the active constituent in these mushrooms and has been shown to inhibit liver aldehyde dehydrogenase. The active metabolite, cyclopropanone hydrate, has also been shown to possess similar activity. This inhibition of ethanol metabolism at the point of aldehyde dehydrogenase results in accumulation of acetaldehyde. In the absence of concurrent ethanol consumption, these mushrooms are edible. 

Phthalyl alcohol, HOCH2CeH4CH20H-o. Mol. wt. 138.16, m.p. 64°. Prepared by reduction of phthalic anhydride with lithium aluminum hydride in ether (87% yield). In a novel and efficient synthesis of cyclopropanone hydrate, Grewe and Struve used the o-xylylene acetal protective group (1) and, after elimination of... 

Schmid KW, Hittmair A, Schmidhammer H, et al. Non-deleterious inhibition of endogenous peroxidase activity (EPA) by cyclopropanone hydrate A definitive approach. J Histochem Cytochem. 1989 37 473. 

Though the symptoms of the biological action of coprine and disulhram are similar, it was demonstrated that the mechanisms of action are different. Contrary to cyclopropanone hydrate, coprine inhibits mouse liver aldehyde dehydrogenase only in vivo but not in vitro. Based on this observation Wiseman and Abeles (429) assumed that coprine itself is inactive in vivo but is activated by hydrolysis to give initially cyclopropanone hemia-minal and ultimately cyclopropanone hydrate. After enzymatic dehydration to cyclopropanone, this compound forms a kinetically stable thiohe-miketal with the enzyme active-site thiols, leading to inactivation of aldehyde dehydrogenase in the enzyme-catalyzed oxidation of acetaldehyde to acetic acid (Scheme 97). 

Toxicity has been associated with the coincident ingestion of the mushroom Coprinius atramentarius along with ethanol. A compound found to the extent of 0.1% by weight of the dried mushroom has been identified as coprine (13). Although coprine itself is inactive in vitro, a derivative of coprine identified as cyclopropanone hydrate was found to be an inhibitor of acetaldehyde dehydrogenase, an enzyme that is involved in the physiological oxidation of ethanol. 

Coprine is a protoxin without intrinsic toxicity, but which hydrolyses to the active toxic principle 1-aminocyclopropanol and cyclopropanone hydrate (cyclopropane-1,1-diol, 10-214). 

Use of Cyclopropanone Hemiacetals. Heating cyclopro-panone hemiacetal at 100 °C in an aqueous buffer provides the cyclopropanone hydrate. It also serves as a source of homoenolate radical species with a catalytic amount of AgN03 (see, eq 15). ... 

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