8- Methoxy-4-methyl-2-quinolone

Japonine (16), the 3-methoxy-4-quinolone of Orixa japonica (see Vol. 2), has beeen synthesized21 (Scheme 2). The key compound (15 R = OMe) was prepared in good yield by the method used to make the analogous 3-hydroxy-4-quinolone (15 R = H) methylation with methyl iodide and potassium hydroxide in DMF then afforded japonine as the major product. 

Hydroxy-2-quinolone is a biosynthetic precursor of quinoline alkaloids (see Section VII), and it is not surprising that compounds of this type occur in rutaceous plants (Volume IX, p. 225). Additional 4-methoxy-2-quinolones with or without N-methyl groups have now been reported. 

Ptelea trifoliata is the only known source of hemiterpenoid quinoline alkaloids containing terminal double bonds, and nine compounds of this type have been isolated cf. Vols. 1—3, 5, and 7) the synthesis of two members of the group, O-methylptelefolonium iodide (26) and ptelefolone (29), has now been reported (Scheme 4). The 3-prenyl-4-methoxy-2-quinolone (24) was prepared by standard procedures and was converted with a peroxy-acid into a mixture of the dihydropyrano-quinolone (25) and the dihydrofuro-quinolone (27), Treatment of the latter with thionyl chloride and pyridine resulted in regiospecific elimination to give a terminal olefin, which afforded O-methylptelefolonium iodide (26). Successive reaction of the N-methyl-4-quinolone (28) cf. Vol. 7) with triphenyl phosphite dichloride and with pyridine resulted in an efficient synthesis of ptelefolone (29). 

The scope of this approach was widened by the observation of excellent enantioselectivities in inter-molecular [2-i2]-photocycloaddition reactions with various alkenes. 4-Methoxy-2-quinolone 27 was converted with high chemo- and regioselectivity to cyclobutanes 29 and 30 in the presence of an excess of alkene. With 4-penten-l-ol 28a, allyl acetate 28b, methyl acrylate 28c, and vinyl acetate 28d, the exo-diastereomers 29a-d were formed with high simple diastereoselectivity and high yields (80 to 89%). Under optimized irradiation conditions (2.4 eq. of host 21 or enr-21,-60"C), high enantiomeric excesses were achieved in all instances, as depicted in Scheme 11 these enantiomeric excesses are unprecedented for an intermolecular photochemical reaction. As in the intermolecular case, host 21 induced Re-attack at carbon C3, and host e r-21 induced a St-attack. 

Recently kinetic data have become available for the nitration in sulphuric acid of some of these hydroxy compounds (table 10.3). For 4-hydroxyquinoline and 4-methoxyquinoline the results verify the early conclusions regarding the nature of the substrate being nitrated in sulphuric acid. Plots of log Q against — (Lf + logioflHao) fo " these compounds and for i-methyl-4-quinolone have slopes of i-o, i-o and 0-97 at 25 C respectively, in accord with nitration via the majority species ( 8.2) which is in each case the corresponding cation of the type (iv). At a given acidity the similarity of the observed second-order rate constants for the nitrations of the quinolones and 4-methoxy-quinoline at 25 °C supports the view that similarly constructed cations are involved. Application of the encounter criterion eliminates the possibilities of a... 

The aposematic beetle, Metriorrhynchus rhipidius, contains three pyrazines as warning odor components and two amides as bitter principles (Tables III, V, and VIII) (97). Of the three components with the beetlelike odor, the most characteristic is 2-methoxy-3-isopropylpyrazine (24b). The other two components are 2-methoxy-3-methylpyrazine (24a) and 2-methoxy-3-sec-butylpyrazine (24d). It would seem likely that these compounds will occur in the defensive systems of the aposematic beetles. The two amide components, detectable in the hemo-lymph exuded by adult beetles, are 3-phenylpropanamide (130) and l-methyl-2-quinolone (57), the latter being the major component. It seems likely that these bitter principles contribute to distastefulness to potential predators. 

The wood of this plant yielded, among other and neutral products, 4-methoxy-l-methyl-2-quinolone (mp 99-103°). The bark yielded nitidine, aricine, chelerythrine, isolated as derivatives, and oxynitidine (mp 283-285°). In addition l-( + )-armepavine metho salt was also found (171). 

Haplopine (1 R1 = H, R2 = OH, R3 = OMe) 4-Methoxy- l-methyl-2-quinolone Robustine Skimmianine... 

Non-hemiterpenoid Quinolines.—New sources of the simple quinolines 4-methoxy-l-methyl-2-quinolone and its 8-methoxy-derivative (folimine) have been reported the former was isolated from Myrtopsis sellingii9 and from Zanthoxylum cuspidatum,16 and folimine was shown to be a constituent of Haplophyllum perforatum.5 The latter species also contains foliosidine (9), previously isolated from H. foliosum. The micro-organism Pseudomonas aertiginosa has been shown to contain 2-(hept-l-enyl)-4-quinolone (12).10 The structure of the alkaloid was established by n.m.r. and mass spectroscopy and by its synthesis from aniline and the j3-keto-ester Me(CH2)4CH=CHC0CH2C02Me. 

Methoxy-l-methyl-2-phenyl-4-quinolone (XXVIII) C17H15NO2 198-200 0 12... 

The UV-spectrum of lunacridine, which is unchanged in acid or alkali, is consistent with the presence of a 2-quinolone system the batho-chromic shift of the maxima at 284 and 294 m/x, in comparison with those of 4-methoxy-l-methyl-2-quinolone (268 and 278 m/a), can be attributed... 

Methoxy-l-methyl-2-quinolone was isolated from the stem bark 132). 

Methoxy-l-methyl-2-quinolone (1) was isolated from Hesperethusa crenulata M. Roem. (12) and from the wood of Fagara boninensis (13). The alkaloid folimine from Haplophyllum foliosum Vved. (14) was identified as 4,8-dimethoxy-l-methyl-2-quinolone (2), which had been obtained earlier during the degradation of foliosine (Volume IX, p. 225). Folifidine from H. dubium Eug. Kor (15) and from H. foliosum (16) is the 8-hydroxy-2-quinolone 3. 

Another 4-methoxy-l-methyl-2-quinolone (10) was isolated from the roots of Spathelia sorbifolia L. (25). The constitution of the alkaloid was established by spectroscopy and confirmed by dimethylation of quinolone 9 with dimethyl sulfate in dimethylformamide. 

Edulinine from Casimiroa edulis may be formed from (+)-N-methylplatydesminium salt during isolation. (+)-Edulinine from Pelea barbigera is certainly an artifact, and was obtained only when base was employed during isolation the precursor, presumably (—)-JV-methyl-platydesminium salt, could not be detected (43). ( )-Edulinine is conveniently prepared by reaction of 4-methoxy-l-methyl-3-(3-methylbut-2-enyl)-2-quinolone with m-chloroperbenzoic acid and then with aqueous base, without isolating intermediates (2). 

In the 8-methoxy series, the (—)-epoxide 109 was treated with diborane-lithium borohydride, and the product (110) of this reaction was cleaved selectively to the 2-quinolone 112 methylation then afforded lunacridine... 

Support for the new mechanism was provided by trapping the intermediate with methyl iodide to give epoxide 133. The structure of this compound was indicated by IR absorption at 1646 cm- (2-quinolone carbonyl) and by the NMR spectrum. The epoxide was converted readily into the diol balfourolone (135) on alumina chromatography or by treatment with 2 N sodium hydroxide at 20° the mild conditions and the failure of 2,4-dimethoxyquinoline epoxides (e.g., 109) to react under similar conditions suggest that this reaction occurs through formation of O-methylbalfourodinium salt (134) and subsequent nucleophilic attack at the 2-position rather than by direct reaction of hydroxide ion on the epoxide ring. Epoxide 133 is the presumed intermediate in reaction of 4-methoxy-... 

Subsequent work was designed to indicate at what point in the pathway methylation of the 4-oxygen function occurs. It was shown by feeding quinolone 322 doubly labeled in the 4-methoxy group and in the side chain that the methoxy group remains intact in the formation of skimmianine in... 

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