Alkylquinolin-4 -ones

A number of reports have confirmed, by NMR, the carbonyl nature of the NH-2-alkylquinolin-4-one unit, indicating the predominance of the NH-oxo forms, which are widely distributed in rutaceous genera, and in Pseudomonas species (Table XI). 

The 2-alkylquinolin/4(l//)-one alkaloids isolated from some bacteria are typical of the Rutaceae. From the systematic standpoint the co-occurrence of 2-n-nonylquinolin-4(l/7)-one in Ruta graveolens, Raulinoa echinata, Boronia bowmanii, 2- -undecylquinolin-4(l//)-one in the former, Ptelea trifoliate (Rutaceae), and both in Pseudomonas (Proteobacteria) is astonishing. In addition, it is noteworthy that many of these alkaloids in bacteria were firmly established as derived from anthranilic acid, while the Rutaceae were less biosynthetically investigated. The analysis of distribution of alkylquinolin/ones among five genera of Proteobacteria division showed that Pseudomonas (Pseudomonadaceae) is the... 

H. L. Holmes, eds.), in The Alkaloids, published by The Chemical Society, London) and subsequently in Natural Product Reports (1-38). In this review, some of the latest developments in the group of natural products collectively known as the alkylquinolin/one alkaloids are presented. Emphasis is placed on their biogenesis, their biological activities, and their natural distribuhon. 

Figure 2 Schematic representation of Waterman s phylogenetic diagram of the Rutales AU Aurantioideae, RU Rutoideae, Rt Rutinae, Cu Cusparieae, Di Diosmeae, Bo Boronieae, Za Zanthoxyleae, To-1, To-2 Toddahoideae, Sp Spathelioideae, Dy Dictyolomatoideae, R Findersioideae, prR proto-Rutaceae (270). (a) Distribution of 2-alkylquinolin/ones, 2-aryl- and 2-alkylarylquinohn/ones. (b) In order to facilitate the analysis the shape representing Rutoideae (RU) was repeated to show the distribution of 2-aryl- and 2-alkylarylquinolin/ones in his tribes.

It is premature to draw any definitive conclusions about the systematic significance of alkylquinolin/ones in bacteria on the basis of the presently insufficient phytochemical data. The above comments are only speculations. 

Table 24.23 Occurrence of Alkylquinolin-4(l//)-one alkaloids in the Rutaceae Species...

Many 2-alkylquinolin/4(l//)-one alkaloids bear the trivial names pseudans because of their occurrence in bacteria of the genus Pseudomonas. For example, P. aeruginosa is a ubiquitous gram-negative bacterial pathogen that causes infections not only in human hosts but also in animals and even plants. 

No data is available on the biosynthesis of 2-alkylquinoline/4(l//)-one alkaloids from anthranilic acid in plant. However, the structures of many alkaloids isolated, especially from the Rutaceae (Tables 24.18,24.23, and 24.24), have provided much indirect evidence for the route proposed at Scheme 24.13. 

Table II Occurrence of alkylquinolin-4(lH)-ones in Rutaceae species jl J... 

Table XI Occurrence of alkylquinolin-4(1H)-ones in fungi, bacteria, and marine organisms... 

The experiments discussed above on the biosynthesis of a pseudan have also shown that kynurenic acid is not the precursor of the 2-alkylquinolin-4(lH)-ones. Based on the putative function of the genes of the qbs operons (176), a pathway was proposed for the biosynthesis of kynurenic acid (I), xanthurenic acid [10(8)], and quinolobactin [IO(8) j in Pseudomonas fluorescens ATCC 17400 (Scheme 5). The first step, the oxidation of tryptophan to N-formylkynurenine, is likely to be catalyzed by the enzyme tryptophan 2,3-dioxygenase (TDO) (QbsF), which is a heme-dependent enzyme. The second step, the deformylation of N-formyl-kynurenine to L-kynurenine is catalyzed by kynurenine formamidase (KFA). The product of qbsH, a metal-dependent hydrolase found also in other bacterial genomes, is the likely candidate. 

Scheme 19 Biogenesis of alkylquinolin-4(lH)-one alkaloids derived from a polyketide...

It is noteworthy that most of the quinolin/ones alkaloids which show high antimicrobial activity are of the 2-alkylquinolin-4(lH)-one type, suggesting that the species cited in Tables 11 and XI should be accorded high priority with respect to further investigation for antimicrobially active alkaloids. 

Chemosystematic comments are of great value if the biosynthesis of the class of compounds in analysis is known, or if the compounds isolated provide evidence for a proposed route. 2-Alkylquinolin-4(lf -ones with an unusual linear aliphatic side chain have been found in the Euphorbiaceae (M) and the Sterculiaceae (MPh.l, MPh.2). They are non-typical quinolones when compared... 

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