Rutaceous alkaloids

In future a third new group will be required, according to another preliminary statement published quite recently by a team of Australian chemists, Messrs. Hughes, Lahey, Price and Webb. They have isolated six alkaloids from three rutaceous species of that country, five of which have been definitely shown to be acridine derivatives. This appears to be the fiipst-fruits of a survey of the type referred to above, which is being carried out on the Australian flora under the auspices of the Council for Scientific and Industrial Research and several of the Australian Universities. ... 

A modification of the formula of a-fagarine just announced establishes its close relationship to the alkaloids of cusparia bark, which like Fagara is derived from a rutaceous genus. ... 

In the course of detailed studies on the chemical constituents of rutaceous plants, genus Xanthoxylum, known to contain the antitumor benzophen-anthridine alkaloids, Ishii et al. (167-173) have isolated four seco amide alkaloids arnottianamide (206), iwamide (207), integriamide (208), and isoarnottianamide (209). Sharma et al. (174) have also found arnottianamide (206) in Toddia Asiatica. 

Tillequin F. (2007) Rutaceous alkaloids as models for the design of novel antitumor drugs. Phytochem Rev 6 65-79. 

Tomita, M. and H. Ishii. 1958. Studies on the alkaloids of rutaceous plants. IV. Alkaloids of Xanthoxylum ailanthoides Sieb. Zucc. [Fagara ailanthoides (Sieb. Zucc.) Engl.]. J. Pharm. Soc. Jpn. 78 1441-1443. 

A new alkaloid, which is structurally related to the cannabinols and named alfileramine (35), has been obtained from the leaves of this Rutaceous plant.34... 

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). 

RUTACEOUS ALKALOIDS OF ESTABLISHED STRUCTURE (see the main work for details)... 

Structures based on the flindersine model are very common in Rutaceous plants and the methoxy-N-methyl derivative (29), is obtained from Oricia renieri (S.A. Khalid and P.G. Waterman, Phytochem., 1981, 20, 2761), while the three alkaloids (30), (31) and (32) come from Vespris stolzii (Khalid and Waterman, J.nat.Prod, 1982, 45, 3il3). 

Quinoline alkaloids are biogenetically derived from anthranilic acid and occur mainly in Rutaceous plants (14). These alkaloids were encountered in Sri Lankan plants of the families Annonaceae and Moraceae, in addition to the Rutaceae. 

Prenylquinolinones and Hemiterpenoid Tricyclic Alkaloids.-3-Prenylquinolinones are well-known constituents of rutaceous plants and are biosynthetic and synthetic precursors of hemiter-penoid quinoline alkaloids all aspects of their chemistry feature... 

Further publications have appeared on the n.m.r. spectra of Haplophyllum alkaloids and on the rearrangement of allyloxy-2-quinolones observed in the mass spectrometer. The mass spectra of rutaceous alkaloids have been reviewed. ... 

Acronycine (1.) is a natural alkaloid which was first isolated in 1948 from the bark of a small Australian Rutaceous tree, Acronychia baueri Schott (1). Since that time, the status of this plant within the Rutaceae family has been revised several times, in the course of successive taxonomic studies (2-5). It is now widely accepted that the plant belongs to the genus Sarcomelicope and should be named Sarcomelicope simplicifolia (Endl.) Hartley ssp. simplicifolia (4). 

In the ten years since quinoline alkaloids were last reviewed by Open-shaw in Volume IX of this treatise, the constituents of a considerable number of rutaceous species have been studied for the first time and more than 70 new quinoline alkaloids have been isolated. The most notable structural work includes the study of the phenolic alkaloids of the dihy-drofuro- and dihydropyranoquinoline group found in Balfourodertdron and... 

Concise general reviews of quinoline alkaloids appeared in 1970 (7) and in 1974 (8), and annual coverage is provided by the Chemical Society, London (9). A review listing in convenient form the occurrence of rutaceous alkaloids up to April 1973 has been published (10). A valuable account of the synthesis of 2,4-dioxyquinoline alkaloids is now available (11). 

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. 

Methoxy-3-prenyl-2-quinolones were first prepared in connection with the synthesis and biosynthesis of quinoline alkaloids (Volume IX, pp. 247, 257), but soon afterward prenyl derivatives were identified as constituents of rutaceous plants (Table I). -Prenyl and O-geranyl ethers without, substituents in the 3-position of the quinoline nucleus will be discussed in Section V of this chapter. 

The occurrence of new furoquinoline alkaloids and their physical properties are indicated in Table VII. N-Methyl-4-quinolones, the so-called isoalkaloids are well known one example is isodictamnine (164), obtained by heating dictamnine with methyl iodide. Isodictamnine, iso-pteleine, isomaculosidine, and isoflindersiamine have now been recognized as constituents of rutaceous species the N-isopentyl alkaloids of Acronychia are also in this category. The alkaloids discussed in this section are grouped in accord with the pattern of oxygenation in the aromatic ring. 

Hydroxy-8-methoxydictamnine (haplopine) has now been found in a number of rutaceous plants (Table I). The alkaloid glycoperine, isolated from Haplophyllum perforatum (M.B) Kar and Kir (175), was shown to be the rhamnoside of haplopine by hydrolysis to L-rhamnose and haplopine. 

Other than evodiamine and rutaecarpine, various alkaloids isolated from Rutaceous plants, such as protoberberine (Section 1.8), quinoline (Section 9.1), and acridone (Section 9.3) alkaloids are sometimes referred to Rutaceous alkaloids. This name, however, refers to a heterogeneous group of alkaloids with diverse biosynthetic origins. 

In the biosynthetic pathway of the alkaloids derived from anthranilic acid, the carbon atom corresponding to the carboxyl carbonyl group is included in the resulting alkaloids, except for those alkaloids with the phen-azine skeleton. The main groups of alkaloids derived from anthranilic acid are classified as quinoline, acridone, and quinazoline alkaloids. These alkaloids are typically isolated from rutaceous plants, except for febrifugine and related alkaloids, which possess the quinazoline skeleton these are isolated from plants of the Saxifragaceae family. 

Among some other quinoline alkaloids, N-methylflindersine was isolated firom rutaceous plants such as O. japonica and Fagara chalybea and showed antifeedant activity against insects Spodoptera exempta) [10]. Eduli-nine, on the other hand, isolated from Zanthoxylum simulans (Rutaceae), was shown to possess analgesic and anticonvulsive activities [11]. 

As described in Section 9.1, quinoline alkaloids have been mainly isolated from rutaceous plants, and very few such alkaloids have been isolated from plants in other families. 

Dimers produced by Diels-Alder reactions between py-ranoquinolone and dihydrofuroquinolone alkaloids occur in a number of rutaceous species. These compounds are known from Araliopsis, Euxylophora, Geijera, Oricia, Ptelea, and Vepris (Waterman, 1986). 

Another Rutaceous plant with a similar alkaloidal spectrum to rue is prickly ash bark—Zanthoxylum spp. Two new quinoline alkaloids isolated from Zanthoxylum simulans were shown to have cytotoxic and antiplatelet activities (Chen et al. 1994). 

Table 24.2 Occurrence of quinolin-2(l/f)-one alkaloids in the non-rutaceous species...

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