title: Alkyl, aryl, alkylarylquinoline, and related alkaloids.
abstract: The Rutaceae continues to be the primary source of new alkyl-, aryl-, and alkylarylquinolin/ones. In the past 17 years, the overall distribution of these alkaloid types within the family has changed little since the chemosystematics reviews by Waterman (270), Mester (40), and da Silva et al. (279). Alkylquinolones dominate the reported isolations with about 51% of the total, with arylquinolones (16%), alkylquinolines (15%), alkylarylquinolines (11%), arylquinolines (3%), alkylarylquinolones (2%), and quinolines (2%) as the significant structural groups contributing to the remainder of this class of alkaloids. The alkyl-, aryl-, and alkylarylquinolin/one alkaloids occur in 50 species belonging to 24 genera and 6 subfamilies. Despite the intensive chemical exploration of many species from other plants in the Rutales family, but not in the family Rutaceae, the first alkaloid alkylquinolone from a simaroubaceous plant (160) was not reported until 1997. Although many additional alkaloids have been reported, some of new structural types (Bo.4), substantial biosynthetic work on plant-derived alkylquinolin/ones has not yet been carried out. The biosynthesis of some of these alkaloids in bacteria was firmly established as being derived from anthranilic acid. Outside of the Rutales, alkyl-, aryl-, and alkylarylquinolin/ones have not been found, except for simple quinoline (A.1; only one) and 2-methylquinoline derivatives in the Zygophyllaceae, and only an atypical quinolone derivative (Ao.1) in the Asteraceae family. A few 3-phenylquinolines (2), 3-(1H-indol-3-yl)quinoline (1), and quinoline-quinazoline (1) alkaloids have been reported from only a single genus in the Zygophyllaceae. Tryptophan-derived quinolines in higher plants are confined to a few 2-carboxylicquinolin/ones (6) and 4-carbaldehydequinolines (5); the former found in the Ephedraceae (5), Boraginaceae (1), Fagaceae (1), Ginkgoaceae (1), Plumbaginaceae (1), Solanaceae (1), and Apiaceae (1), and the latter in the Moraceae (3), Alliaceae (1), and Pontederiacae (1). The number of quinolones derived from glycine and a polyketide is also limited. 5-Alkyl-2-methylquinolin-4(1H)-ones (8) occur in the Euphorbiaceae, and 5-alkyaryl-2-methylquinolin-4(1H)-ones ((3) in the Sterculiaceae. Alkylquinolin/ones are well-known as typical alkaloids of three Proteobacteria and three Actinobacteria; the genus Pseudomonas yielded the majority (46%) of the total number of alkaloids reported (39). 2-Carboxylicquinolin/ones (4) and 4-carbaldehydequinolines (6) are minor constituents in both divisions of bacteria. More interesting are the quinolactacins (7), in which the second nitrogen is derived from L-valine or L-isoleucine, recently reported to occur only in the fungus Penicillium. Many of these diverse alkaloids have served directly as medicines or as lead compounds for the synthesis (258) of derivatives with an improved biological profile. It is apparent from the summary view of the alkyl-, aryl-, and alkylarylquinolin/ones reported in the Rutaceae that they help to confirm the affinity between Rutoideae tribes and provide firm support for placing the Spathelioideae and the Dictyolomatoideae close to the more primitive Zanthoxyleae tribe. On the other hand, the bacteria and fungi are needed for more substantial chemical studies. When more data become available, it is likely that useful systematic correlations will emerge. More detailed studies regarding the biosynthetic pathways of the alkyl-, aryl-, and alkylarylquinolin/ones in the Rutaceae and in bacteria are needed. Such studies would clarify the differences in the pathways based on their derivation from anthranilic acid in bacteria and in rutaceous plants. Finally, this survey indicates that the Rutaceae, and various bacterial and fungal species offer considerable potential for the discovery of new or known alkaloids with significant and possibly valuable biological activities.
authors: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil. dmfs@power.ufscar.br
authors: Maria Fátima das Graças Fernandes
authors: MF
authors: da Silva
authors: Márcio Santos
authors: MS
authors: Soares
authors: João Batista
authors: JB
authors: Fernandes
authors: Paulo Cezar
authors: PC
authors: Vieria
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D008975:Molluscacides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D008975:Molluscacides; D011804:Quinolines