Alkaloids derived from anthranilic acid
Anthranilic acid is an intermediate in the biosynthesis of tryptophan. In addition, a number of alkaloids, mostly found in the Rutaceae, the citrus family, are synthesized from this compound. Small amounts of N-methylanthranilate are found in many essential oils and a simple anthranilic acid-derived alkaloid, damascenine, is found in the seeds of Nigella damascena of the Ranunculaceae.
A number of miscellaneous compounds including DIMBOA and MBOA are discussed under the shikimic acid
pathway.
Quinazoline and pyrroloquinazoline alkaloids
About 60 simple quinazoline alkaloids occur in several plant families, among them are the Acanthaceae (Adhatoda, Araliaceae, Arecaceae, Fabaceae, Hydrangeaceae, Malvaceae, Rutaceae, Scrophulariaceae, and Zygophyllaceae (Peganum). Febrifugine, from the Hydrangeaceae, is a febrifuge and antimalarial. Although about 100 times more effective than quinine, the compound is too toxic for use by humans.
The pyrroloquinazoline alkaloids, such as vasicine, vasicinone, and desoxyvasicinon, occur together in Peganum harmala, Zygophyllaceae. They co-occur with harmine type alkaloids in this genus.
Anthranilic acid is incorporated into vascicine in Adhatoda vasica. The rest of the molecule
may be attributable to aspartic acid.
Quinazolinocarboline alkaloids
More than 20 alkaloids of this group are known, only from the family Rutaceae. Tryptophan, methionine,
formate, and anthranilic acid are all incorporated into rutaecarpine and evodiamine. The dried fruits of
Tetradium (Euodia) rutaecarpa are used in Chinese medicine for treatment of
headaches, abdominal pain, dysentery, postpartum hemorrhage, and amenorrhea.
Quinoline, furoquinoline, and 4-quinolone alkaloids
The largest group of anthranilate-derived alkaloids in the Rutaceae are quinoline, furoquinoline, pyranoquinoline, acridone, and 4-quinolone alkaloids.
Quinoline alkaloids arise by extension of the carboxyl group of anthranilic acid by acetate (malonate) followed by cyclization. These compounds have a 2,4-dioxygenated quinoline stucture.
Furoquinoline and pyranoquinoline alkaloids are based on prenylated quinolone nuclei.
Acridone alkaloids involve extension of the carboxyl group of anthranilic acid by three units of malonate followed by cyclization.
Anthranilic acid may be extended by acetate-derived chains or by phenylpropanoids to yield
4-quinolone type alkaloids.
Quinolone alkaloids
Quinoline alkaloids are primarily known from the Rutaceae. Biosynthesis of these compounds involves anthranilic acid and acetate or malonate.
Occasionally other alkaloid groups have a quinoline type structure, such as those in
Cinchona (Rubiaceae), Tylophora (Asclepiadaceae), and Melochia (Sterculiaceae).
Furoquinoline and pyranoquinoline alkaloids
A number of quinoline alkaloids are subject to prenylation and yield furoquinoline and pyranoquinoline alkaloids. The formation of furoquinoline alkaloids involves formation of the quinoline ring structure before addition of the prenyl group. The furan rings arise by a series of reactions similar to those of furocoumarins. 4-Hydroxy-2-quinoline is a specific precursor to skimmianine in Ruta graveolens.
These two groups of alkaloids occur in four of the five alkaloid-containing subfamilies of the Rutaceae.
Skimmianine intercalates with DNA and undergoes photoaddition reactions with DNA.
Acridone alkaloids
Acridone alkaloids are formed by addition of three acetate (malonate) units to anthranilic acid, followed by cyclization. More than 100 alkaloids of this type are known. They are widespread in the Rutaceae.
Several acridone alkaloids have antitumor activity. Best known among these is acronycine.
4-Quinoline alkaloids
This is a rather rare group of alkaloids. They are known only from a few genera in the Rutaceae.
Pyrroloquinazoline Alkaloids and Vasicine Biosynthesis
Quinazolinocarboline Alkaloids
Quinoline, Furoquinolines, and Pyranoquinoline Alkaloids
Biosynthesis of Furoquinoline Alkaloids
Lecture Slides
Plants with Anthranilic Acid-Derived
Alkaloids
© David S. Seigler, Plant Biology 363, Plant Secondary Metabolism, Department of Plant Biology,
265 Morrill Hall, 505 S. Goodwin Ave., University of Illinois, Urbana, Illinois 61801, USA.
217-333-7577. seigler@life.uiuc.edu.
