Chemicals 3-pyrroline

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pKa of the pyrrolin-ium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted previously in Section 15.5, is that pyrrole has six 77 electrons and is aromatic. Each of the four carbons contributes one... 

In the case of class-II inhibitors, the acyl-enzyme undergoes either normal deacylation (Fig. 5.3, Pathway c) or a chemical re-arrangement in which the enamine tautomerizes to an imine, generating an acyl-enzyme with a A -pyrroline structure (Fig. 5.3, Pathway b). This second acyl-enzyme intermediate hydrolyzes at a much slower rate, and the decreased tum°ver cacis t0 transient inhibition of the enzyme [22] [50]. 

In this type of spin traps, 5,5-dimethyl-l-pyrroline-Af-oxide (DMPO) deserves particular mention. DMPO is widely employed as a spin trap in the detection of transient radicals or ion-radicals in chemical and biological systems (see, e.g., Siraki et al. 2007). Characteristic ESR spectra arising from the formation of spin adducts are used for identification of specific spin species. In common opinion, such identification is unambiguous. However, in reactions with superoxide ion (Villamena et al. 2004, 2007b), carbon dioxide anion-radical (Villamena et al. 2006), or carbonate anion-radical (Villamena et al. 2007a), this spin trap gives rise to two adducts. Let us consider the case of carbonate anion-radical. The first trapped product arises from direct addition of carbonate anion-radical, second adduct arises from partial decarboxylation of the first one. Scheme 4.25 illustrates such reactions based on the example of carbonate anion-radical. 

Chemical reduction of pyrroles by hydriodic acid and phosphorus leads to the formation of pyrrolidines (B-77MI30507) except when the 2-position is substituted by electron-withdrawing groups, which reduce the ease of protonation at the 3-position and, consequently, promote the formation of 2-substituted A3-pyrrolines (cf. Scheme 54) (B-74MI30500, 79MI30504). The analogous reduction of indole-2-carboxamide yields indoline-2-carboxamide (72HC(25-l)l). 

Further reduction of the pyrrolines to pyrrolidines is relatively easy both by catalytic hydrogenation and by metal-acid reduction (see Section 3.05.1.5). In contrast, further hydrogenation of the indolines can only be effected under extreme pressures and temperature to give the octahydroindole, and chemical reduction with hydriodic acid and phosphorus results in cleavage of the five-membered ring (72HC(25-l)i). 

Simple nonconjugated nitrones have a strong absorption maximum in the UV at around 230 nm. Acyclic nitrones are, in general, photo-chemically cyclized to the corresponding oxaziridines.148 The cyclic nitrone, 5,5-dimethyl-l-pyrroline 1-oxide (164) is similarly converted into the oxaziridine (165) by photolysis in ethanol/cyclohexane solution,146 and several 2-substituted 1-pyrroline 1-oxides were subsequently found to undergo the same cyclization in cyclohexane solution.147... 

The selectivity of the trap towards hydroxyl radicals was demonstrated by several control experiments using different radicals, showing that the formation of the respective hydroxylation product, 5-hydroxy-6-0-zso-propyl-y-tocopherol (57), was caused exclusively by hydroxyl radicals, but not by hydroperoxyl, alkylperoxyl, alkoxyl, nitroxyl, or superoxide anion radicals. These radicals caused the formation of spin adducts from standard nitrone-and pyrroline-based spin traps, whereas a chemical change of spin trap 56 was only observed in the case of hydroxyl radicals. This result was independent of the use of monophasic, biphasic, or micellar reaction systems in all OH radical generating test systems, the trapping product 57 was found. For quantitation, compound 57 was extracted with petrol ether, separated by adsorption onto basic alumina and subsequently oxidized in a quantitative reaction to a-tocored, the deeply red-colored 5,6-tocopheryldione, which was subsequently determined by UV spectrophotometry (Scheme 23). 

By coincidence, at the time the first report on ferropyrimine appeared work was in progress in France on the chemical nature of the pigment from Marchal s organism, which was named ferrorosamine (100). The latter was isolated as an amorphous powder from which distillation yielded a base, 2-(2 -pyridyl)-l-pyrroline. The complex formed with Fe2+ greatly... 

The chemical shift of the A-pyrroline methyl group in the cyclazine (17) was diagnostic, occurring at 51.67 instead of in the 52.2-2.6 range observed for pyrrole methyl groups... 

Many pyrrolizidine alkaloids are metabolized to toxic pyrrole metabolites in the liver by mixed-function oxidases. The structural and chemical features necessary for the formation of these metabolites have been discussed.77 The most important features, in addition to the 3-hydroxymethyl-3-pyrroline system, are steric hindrance to hydrolysis of the ester, lipophilic character (favouring attack by the hepatic microsomal enzymes), and the presence of a conformation that allows preferential oxidation of the pyrroline ring rather than 7V-oxidation. The alkylating activities of a series of these pyrrole derivatives have been examined.78... 

Metabolic N-demethylation of methadone occurs since incubation of levo methadone with rat liver slices results in the formation of formaldehyde at a rate only marginally less than that obtained with pethidine as substrate. °2) The reason for the failure of early attempts to isolate the corresponding secondary amine is now well established as due to the facile cyclization of N-desmethylmethadone to a pyrroline derivative. Chemical studies have confirmed the cyclic structure 3 (13) the corresponding free base is an exocyclic alkene 2 that exists as an approximately 50 50 mixture of c-t isomers.(14)... 

Analytical-grade reference compounds and solvents were obtained commercially (Aldrich Chemical Co., St. Louis, MO), except ( )-P-Damascenone was provided by Firmenich Co. (Princeton, NJ) and 2-acetyl-1-pyrroline was a gift from Dr. R. Buttery (USDA, ARS, WRRC, Albany, CA). Dimethyltetrasulfide was synthesized using a published procedure (72). Reagents used for amino acid analyses were obtained from Beckman Coulter, Inc. (Fullerton, CA). 

Figure 8.17. Chemical structures of A-heterocycles responsible for mousy off-flavor of wines (8) 2-acetyl-l-pyrroline (APY), (9) 2-acetyltetrahydropyridine (ATHP), (10) 2-ethyltetrahydropyridine (ETHP).

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