Anthranilate alkaloids

In contrast, the Toddalioideae seems to exhibit a markedly reduced ability to produce 2-substituted anthranilate alkaloids. The co-occurrence of Bo and Do in the genera of the Zanthoxyleae, Ruteae, Boronieae (except Do), Cuspaiieae, and Toddalieae (Figure 2 Table XII) suggests some affinity between the Rutoideae and Toddalioideae. 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

The alkaloid rutaecarpine (111) was synthesized from l-oxo-1,2,3,4-tetrahydro-)3-carboline (183 R = H) by condensation with methyl anthranilate in the presence of phosphorous chloride or by heating... 

It should be also noted that, in a very recent publication, Liu and coworkers were successful in applying microwave radiation within their domino approach towards the synthesis of pyrrolo[2,l-fc]quinazoline alkaloids such as deoxyvasicinone, 8-hy-droxydeoxyvasicinone, mackinazolinone and isaindigotone, which exhibit a promising broad spectrum of biological activities. In the case of isaindigotone, the authors were able to extend their strategy to a three-component procedure, which comprises the domino conversion of anthranilic acids and Boc-protected amino acids into the tricyclic core skeleton [43]. 

The route of formation of the carbazole nucleus is still far from understood, and has been variously considered to arise from 3-prenylquinolone via a pathway involving shikimic acid (394) and mevalonic acid (MVA) (400) (Scheme 3.1) (1,112,362-366), anthranilic acid (397) and prephenic acid (404) via a pathway involving shikimic acid (394) (Scheme 3.2) (367), and also tryptophan (408) involving the mevalonate (400) pathway (Scheme 3.3) (133). All of these pathways lack experimental proof. However, based on the occurrence of the diverse carbazole alkaloids derived from anthranilic acid (397) in the family Rutaceae, the pathway... 

Figure 13. L-anthranilic acid is a precursor of quinazoline, quinoline and acridine alkaloids.

Anthranilic Anthranilic acid-derived True alkaloids... 

Figure 28. The nuclei produced by anthranilic acid in alkaloids.

Alkaloids derived from L-tryptophan hold the indole nucleus in a ring system. The ring system originates in the shikimate secondary compounds building block and the anthranilic acid pathway. It is known that the shikimate block. 

The second type of quinohne alkaloid, found especially found in the Rutaceae family, has a as anthranilic acid. Typical compounds from this group are eduli-tine, halfordamine, folifidine, folinine, casimiroin, fohosidine and swietenidine. The /3 is 3-carboxyquinoline and the A is graveoline in the case of those alkaloids from Ruta angustifolia. 

Quinoline alkaloids from the Rutaceae family (a = L-anthranilic acid) show antimicrobial activity. Moreover, quinoline alkaloids of the Haplophyllum species are known for their powerful biological properties. For example, skim-mianine has sedative, hypothermic and antidiuretic uses. Haplophyllidine is a strong depressant of the CNS. 

Evodia rutaecarpa (Juss.) Berth Wu Zhu Yu (Evodia) (fruit) Alkyl methyl quinolone alkaloids, evodiamine, limonin, evocarpine, rutaecarpine, N-methyl anthranilic acid, evodol, hydroxyevodiamine, N-methylanthranflamide, N,N-dimethyl-5 -methoxytryptamine, dehydroevodiamine.32,33,237 Antiemetic, analgesic, lower blood pressure, antibacterial. 

There are several classes of alkaloids. Among these are purines such as xanthine and caffeine, ter-penes (Chapter 22), polyketides (Chapter 21), and alkaloids derived from amino acids. The basic amino acids ornithine, arginine, histidine, and lysine as well as the aromatic amino acids, anthranilate, and nicoti-nate are some of the starting materials.199 201 Robinson202 203 in 1917 recognized that many alkaloids are derived directly from aromatic amino acids. He proposed that alkaloids arise from Mannich reactions (Eq. 25-12) in which an amine and an aldehyde (probably through a Schiff base) react with a nucleophilic carbon such as that of an enolate anion. Many of the... 

Anthranilic acid (2-aminobenzoic acid) (see page 126) is another shikimate-derived compound which, as its CoA ester anthraniloyl-CoA, can act as a starter unit for malonate chain extension. Aromatization of the acetate-derived portion then leads to quinoline or acridine alkaloids, according to the number of acetate units incorporated (Figure 3.47). These products are similarly discussed elsewhere, under alkaloids (Chapter 6, page 376). 

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