Aristolochic acid structure

Aristolochic acids, representatives of the substituted 10-nitrophenanthrene-l-acids, have been known since 1943, when Rosenmund and Reichstein first isolated aristolochic acid I (1) from A. clematitis (23) [this compound was named aristolochic acid A by Tomita and Sasagawa (24)]. Its structure was elucidated by Pailer et al. in 1956 by means of chemical reactions (25), and when several aristolochic acids—aristolochic acids II (2) (aristolochic acid B by Tomita), III (3) Ilia (4) (aristolochic acid C by Tomita), IV (5), and IVa (6)—were isolated from the root of A. clematitis by Pailer and his co-workers (26) and in the meantime from A. debilis and A. fangchi by Sasagawa (27). 

Aristolochic acid derivatives have been found only among plants of the family Aristolochiaceae (Aristolochia spp. and Asarum canadense var. reflexum (34)) and in Bragantia wallichii (35,36). In all derivatives, substitution of nitro group is present at C-10, the carboxy group is present at C-1, and a methylenedioxy is substituted at C-3 and C-4 only. This general structure will be very interesting in biosynthesis and plant biochemistry. 

The structural determination of aristolochic acid I (1) was first accomplished by Pailer et al. Aristolochic acid I(Ci7Hn07N) is easily soluble in alkali as well as sodium bicarbonate. It was esterified with diazomethane in dioxane to give a methyl ester (C,gHi307N), and the methyl ester was readily saponified to recover aristolochic acid I. Zinc distillation of 1 gave a phenanthrene (Scheme 6). Aristolochic acid I was decarboxylated with copper powder in quinoline to yield a nitro phenanthrene derivative (OjgHjjOjN.Sl). 

The structure of aristolochic acid II (2) was determined by Pailer and Schlep-pnik in the same way as aristolochic acid I. Decarboxylation of aristolochic acid II gave a nitro compound (62). Oxidation of 62 and cleavage with HCl formed... 

After the elucidation of the structure of aristolochic acid I, several related compounds, such as aristolochic acids III, Ilia, IV, and debiiic acid, were determined in the same way by Pailer (26), Pailer and Bergthaller (75), Tomita and Sasagawa (24), and Tseng and Ku 29,76,77). 

Balachandran P, Wei F, Ein RC, Khan lA, Pasco DS. Structure activity relationships of aristolochic acid analogues toxicity in cultured renal epithelial cells. Kidney Int 2005 67 1797-1805... 

Fig. 3 Structural diversity of bitter compounds. The chemical structures of absinthin, aristolochic acid, denatonium, strychnine, D-(-)-salicin, and phenylthiocarbamate (PTC) are depicted. Note the different sizes, charges, and three-dimensional architectures of these compounds that all activate at least one of the human bitter taste receptors...

Over the last seventy years over sixty species of Aristolochia have been exploited for chemical examination by research groups throughout the world and a variety of compounds have been isolated. The spectrum of physiologically-active metabolites from Aristolochia species covers 14 major groups based on structure aristolochic acid derivatives, aporphines, amides, benzylisoquinolines, isoquinolones, chlorophylls, terpenoids, lignans, biphenyl ethers, flavonoids, tetralones, benzenoids, steroids, and miscellaneous. The aristolochic acid derivatives, host of phenanthrene derived metabolites were further classified into aristolochic acids, sodium salts of aristolochic acids, aristolochic acid alkyl esters, sesqui- and diterpenoid esters of aristolochic acids, aristolactams, denitroaristolochic acids, and aristolactones. The terpenoids can further be subdivided into 4 groups mono-, sesqui-, di- and tetraterpenoids. 

Fig. (1). The Structures of Sesqui- and Diterpenoid Esters of Aristolochic Acids...

The striking structural kinship of the aristolochic acid skeleton with that of the aporphine alkaloids suggested a biogenetic relationship. The... 

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). 

The structural elucidation of the yellow colored aristolochic acid-I was carried out in the 1950s mainly by Pailer and his students. The main degrada-... 

Scheme 11.53. A cartoon representation of a potential pathway to aristolone from farnesyl diphosphate.The pattern of methylation anticipated has changed due to (presumably) a series of hydride and methide shifts. The structure of aristolochic acid, one of the few nitro-containing natural products known is also shown since some sesquiterpene alcohols are found as esters.

Fractionation of extracts of Aristolochia indica have furnished [155-157] the tumour inhibitory principle aristolochic acid I (XXXVIa). Its structure was deduced by chemical methods, and was confirmed by a novel synthesis [158], Piperonal was converted to the nitro-ester (XXXVII) in 8 steps, and condensation of this compound with the iodo aldehyde (XXXVIII) derived from... 

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