4-Quinolinones

Most often naturally occurring quinolin-2-ones are found In the Rutacea and all the alkaloids listed below arise in plants of this family. 

The swietenidins A and B, which are the first naturally occurring 2-quinolinones to bear a methoxyl group at C-3, are present in the bark of the East Indian satin wood Chloroxylon swietenia. Their structures, (17) and (18) respectively, were deduced from spectroscopic data 

Structure (20) for daurine is supported by the fact that it may be degraded to the known alkaloid folifidine (21). 

The roots of another plant in this genus - G. mauritiana metabolise the related but unnamed structure (25) (K. Rastogi, R.S. Kapil and S.P. Popli, Phytochem., 1980, 19, 945). 

Almeine (26), amorphous, and M-desmethyl-N-methylatanine (27), m.p. 162-163°C, are present in the stem bark of Almeidea guyanensis (C. Moulis et al, Phytochem., 1983, 22, 2095). Treatment of the latter compound with DDQ gives rise to N-methylflindersine (28), m.p. 84°C, which occurs in the root bark of Ptelea trifoliata (J.Reisch et al., ibid., 1975, 14, 1678), and which is also the insect antifeedant 

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The alkaloid dubamine contains a single bond between the two heteroarene units. This lond was formed in 79% yield by the generally valuable palladium-catalyzed eoupling of an ryltrimethylstannane with an aryl triflate (see section 1.6). The requisite stannane was pre-ared from l,3-benzodioxol-5-yl triflate and hexamethyldistannane with the same palladium atalyst, the triflate ester was obtained from 2(1 f/)-quinolinone and trifluoromethanesulfonic jihydride (A.M. Echavarren, 1987). An earlier attempt to perform this aryl coupling by dassical means gave a yield of only 1 %. 

Since polar solvents would be expected to stabilize polar forms, a retreat towards the hydroxy tautomer (71) would be predicted in solvents less polar than water, and in the vapour phase. This is borne out in practice at equilibrium both 2- and 4-hydroxypyridine (as well as the 3-hydroxy compound, which even in water exists as an approximate 1 1 mixture of OH and NH forms) exist as such, rather than as the pyridinones. However, the 2- and 4-quinolinones remain in the NH (keto) forms, even in the vapour phase. Hydrocarbon or other solvents of very low polarity would be expected to give results similar to those in the vapour phase, but intermolecular association by hydrogen bonding often leads to a considerably greater proportion of polar tautomers being present than would otherwise have been predicted (77ACR186, 78JOC177). 

Pyrimido[4,5-6]quinolinium salts pseudo bases - ring opening, 3, 208 Pyrimido[4,5-6]quinolinium salts, 4-chloro-hydrolysis, 3, 214 Pyrimido[4,5-6]quinolinones synthesis, 3, 228 Pyrimido[4,5 -6]quinolin-5-ones synthesis, 3, 221-222 Pyrimidothiadi azoles reactions, 6, 533 Pyrimidothiazines synthesis, 4, 527 Pyrimidothiazinones mass spectra, 2, 23... 

Isomeric 4,5-dihydro[4,5-/]derivative 76 has been prepared from 7,8-dihydro-5(6//)-quinolinone via a semicarbazone and its subsequent reaction with thionyl chloride (95JHC177). 

Selenium dioxide oxidation of 7,8-dihydro-5(6//)-quinolinone semicarbazone gave, in addition to the expected 4,5-dihydro selenadiazoloquinoline 95 (analogous to sulfur derivative 76), the oxidized l,2,3-selenadiazolo[4,5-/]quinoline 96, which, when heated to 210°C for 30 min, gave the dimeric [l,4]diselenino [2,3-/ 5,6-/ ]diquinoline (95JHC177). 

Treatment of the pyrrolidine derivative 130 with sodium hydride followed by A-methyl piperazine afforded pyrrolidino[l,2-a]quinolinone 4-carboxy-late 131 (93JPR397) (Scheme 25). 

Lewis-acid-catalyzed Diels-Alder reaction of 3-phenylthio-2- quinolinones with silox-ydiene. Synthesis of the intermediate for dynemicin A core [97]... 

CN (R, S )-8-hydroxy-5-[]-hydroxy-2-[(l-methylethyl)amino]butyl]-2(l//)-quinolinone... 

The 5,8-dimethoxy-2(l//)-quinolinones 60 were obtained in moderate yield via an intramolecular Wittig reaction <95LA1895>. 

The ort/to-directing effect of the carbonyl group in the regioselective lithiation of 2( 1/f) quinolinone has been studied by Avendano <9581362>. 

The term benzodiazepine refers to a specific chemical structure. Numerous benzodiazepine-receptor ligands exist which have different structures. These include the jS-carbolines (e.g. methyl-6,7-dimethoxy-4-ethyl-jS-carboline 3-carboxylate DMCM), triazolopyridazines (e.g. CL 218872), imidazopyridines (e.g. zolpidem), and pyrazolo-quinolinones (e.g. CGS 8216). In experimental animals these compounds produce... 

The antiulcer agent rebamipide ((2-(4-chlorobenzoy-lamino)-3-[2(lH)-quinolinon-4-yl]propionic acid) dose-dependently decreased hydroxyl radical signal generated by the Fenton reaction in an e.s.r. study. Rebamipide is active as a hydroxyl radical scavenger and inhibitor of superoxide production by neutrophils (Yoshikawa etal., 1993). 

Figure 23 sketches these four pathways, namely the 5,6-dihydroxy-2(lH)quinolinone pathway, the 7,8-dihy-droxy-2(lH)quinolinone pathway, the anthranilate pathway, and the 8-hydroxycoumarin pathway. 

As can be seen, in both the 5,6- and the 7,8-dihydroxy-2(lH)quinolinone pathways, after initial hydroxylation adjacent to the N-heteroatom, the benzene moiety of the quinoline ring is transformed to a dihydroxy derivative 5,6- or 7,8-, respectively, which subsequently undergoes ring cleavage. However, neither of them involves C—N bond cleavage and consequently do not lead to denitrogenated products. 

Methylquinoline (2) 3-methyl-2(lH)quinolinone (3) 5,6-dihydro-5,6-dihydroxy-3-me thy 1-2(1 H)quinolinone (4) 6-hydroxy-3 -methyl-2( 1 H)quinolinone (5) 5,6-dihydroxy-3-methyl-2(lH)quinolinone (6) 3-methyl-2,4,6-trihydroxypyridine (1) 4-Methylquinoline (2) 4-methyl-2(lH)quinolinone (3) 7,8-dihydro-7,8-dihydroxy-4-methy 1-2(1 H) quinolinone (4) 8-hydroxy-4-methyl-2(lH)quinolinone (5) 7,8-dihydroxy-4-methyl-2(1 H)quinolinone (6) 6-hydroxy-5-(2-carboxyethenyl)-4-methyl-2( 1 H)pyridone... 

Quinaldine (2-methyl-quinoline) (2) 2-methyl-4(lH)-quinolinone (3) 3 -hydroxy-2-methyl-4( 1 H)quinolinone (4) N-acetylanthranilic acid (5) Anthranilic acid (6) Catechol (1) Quinoline (2) 2(lH)quinolinone (3) 8-hydroxy-2(lH)quinolinone (4) 8-hydroxycoumarin (5) 2, 3-dihydroxyphenylpropionic acid... 

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