Simple Quinolines and Quinolones

With the sole exception of the quinolylimidazole alkaloids, all the alkaloids described in this chapter occur exclusively in members of the Rutaceae Price (2) has discussed the taxonomic significance of the distribution of these and other alkaloids within this family. A summary of the chemistry of all the rutaceous alkaloids has been published (3). 

A number of simple quinolines and quinolones have been isolated from various rutaceous plants, e.g., from angostura bark (Volume III, p. 80) and from Lunasia amara Blanco (Volume VII, p. 241 this chapter Section IV,A). The leaves of Haplophyllum dubium Eug. Kor (15, 16) contain dubamine (mp 96°-97°) which has been identified (17) as 2-(3,4-methylenedioxyphenyl)quinoline (I). Ruta graveolens L. contains, in addition to furoquinolines, the alkaloids graveoline (mp 205°) (18,19), and graveolinine (mp 115°-116°) (20), the latter (II) is also found in L. amara, and the former is the related l-methyl-4-quinolone (III). 

The seed (21) of the Mexican tree Casimiroa edulis Llave et Lex. contains eduline (IV) (mp 187°-188°), identified by synthesis (22), the 

A somewhat more complex 4-methoxy-2-quinolone is the alkaloid foliosidine (VIII) (inp 141°-142°) from Haplophyllum foliosum Vved. (see Section VI). The 2,3-dihydroxyisopentyloxy side chain, also found in evoxine and maculosine, was shown to be present by periodic acid oxidation to acetone and an optically inactive aldehyde. 

On heating with alkali, the side chain was eliminated, leaving an optically inactive phenol w hich on methylation yielded 4,8-dimethoxy- 

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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. 

Simple quinoline alkaloids have been isolated from several genera - e.g., 4-methoxy-l-2-quinolone from Fagara boniensis, and edulitine from Casimiroa edulis. 

Anthranilic acid and acetate biosynthesize the simple quinoline alkaloids, which are then prenylated with mevalonic acid at the C-3 position to 3-prenyl-2-quinolone alkaloids (e.g., pterecortine from Ptelea trifoliata and orixine from Orixa japonica). 3-Prenyl-2-quinolone alkaloids are then cyclized to dihydrofuro-or dihydropyranoquinoline alkaloids. Hydroxylation at the C-3 position of dihy-drofuroquinoline alkaloids and subsequent loss of the isopropyl side chain produce the furoquinoline alkaloids (Fig. 5.2.8) dictamnine is a skeletal alkaloid and skimmianine is the most common alkaloid. 

In addition to reaction catalysts, a number of quinolines were described with valuable chemo-sensing properties. Even a simple quinolone, such as that shown in Scheme 1, can be used as a method for cyanide detection in aqueous environments (14TL1052).This quinoline-derived probe with an aldehyde forms a cyanohydrin with strong fluorescence. Another quinoline chemosensor, a quinoline tripodal thiourea, selectively binds with fluoride and no other halogens (14TL1467). A thioamide-based sensor with both... 

As shown in Scheme 1.46, a simple synthesis of complex fused 1,4-benzoxaz-epin-2-one derivatives 86 and 87 was aehieved via a three-component leaction of quinoline or isoquinoline, acetylene dicaiboxylic esters and l-(6-hydioxy-2-isopio-penyl-l-benzofman-yl)-l-ethanone in water, in the absence of aiy catalyst [68]. Presumably, this transformation proceeds via the initial formation of a 1 1 zwitter-ionic intermediate 88 from the Michael addition of isoquinohne (or quinolone) to the activated ester. A proton transfer reaction takes then place in which this species is protonatedby the phenol group in the l-(6-hydroxy-2-isopropenyl-l-benzofuran-yl)-l-ethanone substrate, and this is followed by a second Michael addition of the resulting phenoxide anion to the isoquinohnium ion to afford intermediate 88, containing benzofuryl and isoquinoline ring systems. This intermediate then undergoes... 

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