Aristolochic acid derivative alkaloids

VIII ARISTO Aristolochic acid derived alkaloids... 

The plant is known elaborate a series of quite unusual phenanthrene alkaloid derivatives, of which aristoliukine-C, aristofolin A and E, aristolochic acid-la methyl ester, and aristolochic acid. Other chemical constituents found in this plant are flavonoid glycosides such as kaempferol-3-O-rutinoside and quercetin kaempferol-3-O-rutinoside (3,4). Exposure to Aristolochiaceae family is associated with the development of cancer in humans. A significant advance is the toxicological effects of aristolochic acid has been provided by the work of Pezzuto et al. They showed that aristolochic acid is a mutagen... 

The IR spectra are useful for detecting functional groups of Aristolochia alkaloids. Aristolochic acids show two characteristic bands at 1550 and 1350 cm due to the absorption of nitro group, and the carboxy OH group appears at 3000-2500 cm as a broad continuous absorption. Hydroxy derivatives of aristolochic acids or aristolactams show OH and NH absorptions at 3300-3500 and 3200-3400 cm The carboxy or lactam carbonyl is present at 1690 cm i. In general, the aromatic ring system shows stretches at 1625-1575 and 1525-1475 cm 1 as usual, and observation of the 900-700 cm region is often used for analysis of substitution type in aromatic derivatives 28). 

The term aporphinoids covers aporphines and their close biogenetic precursors, the proaporphines. Alkaloids derived from relatively straightforward biological transformations of proaporphines or of aporphines are also encompassed, so that proaporphine-benzylisoquinolines, aporphine-benzylisoquinolines, aporphine-pavines, oxoaporphines, dioxoaporphines, aristolactams, and aristolochic acids, as well as phenanthrenes, will be discussed. Azafluoranthenes are also included within the scope of aporphinoids for reasons which will become clear toward the end of the present chapter. 

Aristolochic acids and aristolactams possess skeleta (66) and (67), respectively, and are often found in the same plant. The aristolochic acids are among the small group of natural products incorporating a nitro-function. Compounds belonging to these two classes are non-basic, but can nevertheless be classified as alkaloids since they are derived from in vivo oxidation of aporphines. The last review on this dual topic appeared in 1961. ... 

In the case of the phenanthrine derivative aristolochic acid-I, the skeleton is derived from an aporphine alkaloid precursor which has undergone oxidation, to the point where the nitrogen atom exists as a nitro group. Biosynthetically, this compound is also classed as an alkaloid. 

This group of alkaloids is known primarily from the genus Aristolochia (Aristolochiaceae). Several of the compounds contain nitro groups. Despite their unusual structures, aristolochic acids are derived from benzylisoquinoline precursors. Alkaloids from the genus Aristolochia (Aristolochiaceae) have been reviewed (Chen and Zhu, 1987). 

Aristolochic acids (46) and the related aristolactams are thought to be derived from aporphine alkaloids, although there is little experimental evidence to support this proposal. Tyrosine, DOPA, and noradrenaline are precursors. A biosynthetic pathway has been proposed (Fig. 32.15) (Cordell, 1981). 

Phenylalkylamines. isoquinoline alkaloids, amaryllidaceae alkaloids, aristolochic acids, melanins, gliotoxin, betalains, thyroxine, cinnamic acids, coumarins. lignins, lignans, benzoic acids, stilbenes. flavonoids, hydroquinone derivatives etc.. 

Aristolochic acids, nitrocompounds found in Aristolochia species, are derived from aporphine-type alkaloids by oxidative degradation (Fig. 288). Probably intermediates are involved which are hydroxylated at position 4. Aristolochic acids are taken up with the diet by larvae of butterflies feeding on Aristolo-chiaceae. They protect the animals from potential predators (E 5.1). 

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