Rutaceae, acridone alkaloids

Fewer than 100 acridone alkaloids are known. Typical compounds include, for example, atalaphylline, acronycine and preacronycine. Acridone alkaloids occur in plants and animals. They are especially characteristic of the Rutaceae plant... 

The acridone alkaloids constitute a small group of natural products found exclusively in the Rutaceae family of higher plants. A sustained interest in this field has been due to the reported activity of acronycine a constituent of Acronnychia baueri and Vepris amphody as an anti-tumor agent. 

Acridone alkaloids comprise a relatively small group of alkaloids that are found solely in some Rutaceae genera. Some 100 examples of this alkaloid group have been isolated and these include the monomeric acridones and the acridone-coumarin dimers (acrimarines) isolated from Citrus plants some binary alkaloids have recently been isolated and described (Takamura et al, 1995). 

Binary furanoacridones constitute a rare group of acridone alkaloids found restricted thus far to the Sri Lankan Rutaceae, Atalantia ceylanica. Two novel binary furanoacridones, atalanine (21), C34H30N2O9, mp 216.5-217.5°C, and atahne (22), C38H34N20O9, mp 209-210°C, were isolated from this plant and their structures were elucidated with the aid of spectroscopic... 

Acronycine was isolated from the bark of the Australian scrub ash, Baurella simplicifolia =Acronychia baueri) (Rutaceae), together with related alkaloids [1]. Acronycine is classified as an acridone alkaloid, and acridone is an oxidized derivative of acridine. Acridine itself was isolated from coal tar in the nineteenth century, but the isolation of acronycine and related alkaloids was the first occasion that the acridine (acridone) unit was isolated from a higher plant. 

Table 24.11 Occurrence of acridone alkaloids in O 8 N 1 A ll = 1 R Rutaceae 1 1 1 4 species...

Table 24.17 Occurrence of dimeric acridone alkaloids in Rutaceae species...

No data is available on the biosynthesis of dimeric acridone alkaloids, which have been found in Rutaceae. Acridone-coumarin/xanthone/Ugnin dimers have also been found in Rutaceae (Table 24.17). The bark of the New Caledonia tree Sarcomelicope megistophylla (Rutaceae) have yielded an intriguing range of... 

Happi EN, Waffo AFK, Wansi JD, Ngadjui BT, Sewald NS (2011) I-prenylated acridone alkaloids from the stems of Balsamocitrus paniculata (Rutaceae). Plant Med 77 934-938... 

Acridone alkaloids (49) were first isolated from the bark and leaves of some Rutaceae species in Australian tropical rain forests. The best known acridone alkaloid, acronycine, was obtained from the bark of Acronycia bauri together with the related alkaloids (noracronycine, de-A/-methylacronycine, and de-A/-methyl-noracronycine) and simple acridone alkaloids (l,3-dimethoxy-A/-methylacrydone, melicopine, melicopicine, etc.). Acronycine displayed significant activity in several tumor test systems and it was reported to be orally active. 

In regard to the antineoplastic properties of Rutaceae, this family has attracted a great deal of interest for its ability to elaborate series of cytotoxic benzo[c]phenanthri-dine and acridin alkaloids. Examples of acridin alkaloid are pyrano-acridone and acronycine characterized from Acronychia baueri Scott. 

Addendum. A comprehensive review on the occurrence of alkaloids in the Rutaceae family has appeared. The broad spectrum of alkaloid types, including quinolines, furoquinolines, and acridones, may be appreciated from the list of species given in this review. 

The alkaloids melicopicine from Melicope fareana [86], acronycine from Acrony-chia baueri [87, 88], and rutacridone from R. graveolens (Rutaceae) typify some of the structural variety that may then ensue. For instance, radioactivity biosynthetic studies on R. graveolens, using [1- H]DMAPP (dimethylallyl diphosphate), demonstrated that 1,3-dihydroxy-A-methylacridone reacted with DMAPP upon mediation of a monoprenyl aryl transferase. The formed prenylated acridone glycocitrine-H in turn cyclized to give the dihydrofuran portion of rutacridone. Compounds 21 and 22 are hypothetical intermediates (Figure 6.18) [89]. 

The biosynthetic pathway to rutacridone, which was isolated from Ruta graveolens (Rutaceae), was studied in detail using the cell culture method [4,5]. According to these results, the biosynthetic precursors of rutacridone are anthranilic acid, acetic acid, and an isopentenyl unit, as in the case of the quinoline alkaloids described in the previous section. However, in the biosynthesis of rutacridone, two additional C2 units participate in the biosynthesis of the acridone nucleus compared with the biosynthesis of quinoline alkaloids. 

In addition to the relatively simple anthranilic-derived metabolites mentioned above, several distinctive types of alkaloids are derived from this amino acid. Most of these are associated with the Rutaceae and related families of the Rutales. Among these groups of alkaloids are the quinazoline, pyrroloquinazoline, quinazolinocarboline, quinoline, furoquinoline, and acridone types. 

The Rutaceae is one of the most interesting families in regard to alkaloid chemistry as well as the formation of fla-vonoids, mono-, sesqui-, and triterpenes, furocoumarins, and other secondary compounds (Waterman and Grundon, 1983). Many chemical features support the view that the Rutaceae is a distinct and homogenous group. Essential oils and coumarins are found in at least four subfamilies. Furo-quinoline alkaloids are essentially ubiquitous in the family, and acridones are common. 

Waffo AFK, Goombes PH, Grouch NR, Mulholland DA, El Amin SMM, Smith PJ (2007) Acridone and furoquinoline alkaloids from Teclea gerrardii (Rutaceae Toddalioideae) of southern AMca. Phytochemistry 68 633-667... 

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