Alkaloids, acridine

Three reports in 1989 and 1990 described the structures of three closely related acridine-derived alkaloids. Isolations were from a tunicate, a sponge, and, interestingly, a tunicate and its prosobranch mollusc predator. 

Shermilamine A-B. The first of the acridine-derived alkaloids to be reported were shermilamine A and B (32) (Carroll et al. 1989). Using long-range 

Nordercitin, Dercitamine, Dercitamide, and Cyclodercitin. A series of three pyridoacridine alkaloids related to the shermilamines were reported by Gunawardana et al. (1989). In assigning the structures of nordercitin (R = NMe2) dercitamine (R = NHMe), and dercitamide (R = NHCOEt) (33), isolated from two deep-water marine sponges of the family Pachastrellidae, the authors used a combination of COLOC and HMBC spectra. The report did not compare results of the two experiments nor unfortunately did it 

A fourth pyridoacridine alkaloid, cyclodercitin, was also described in the report. The alkaloid was poorly soluble in methanol-d4 and correlations could not be observed from the methylene resonances in an HMBC spectrum. Cyclodercitin did, however, readily dissolve in TFA-d, albeit with conversion of the pyrrolidine to afford the corresponding pyrrole, 34. Correlations were observed from the H9 resonance of the pyrrole to C7a and C13d, confirming the site of fusion of the pyrrole to the pyridoacridine nucleus. 

Kuanoniamines A-D. The third group of acridine-derived alkaloids to be reported, was the kuanoniamines (35, 36) (Carroll and Scheuer 1990) isolated from a Micronesian tunicate and its prosobranch mollusc predator Chelynotus semperi. Structurally, the kuanoniamines differ from nordercitin and the related compounds discussed above only in the fusion of the thiazole to the pyridoacridine nucleus. Direct proton-carbon shift correlations were 

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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. 

Examples of acridin alkaloids used in therapeutics as antineoplastic agents is amsacrine (Amsa P-D ), which is used for the treatment of acute leukemia in adults and malignant lymphomas, refractory to conventional therapy. Amsacrin is an intercalating agent and topoisomerase II inhibitor. 

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

Dercitin (464) is a violet acridine alkaloid from a deepwater species of Dercitus with antitumour, antiviral and immunomodulatory properties in vitro [389] and with in vivo antitumour activity [390]. The structure was proposed on the basis of spectral properties. Cyclodercitin (465) was isolated as a minor alkaloid from a deepwater Dercitus species and three... 

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). 

The polyketide synthases responsible for chain extension of cinnamoyl-CoA starter units leading to flavonoids and stilbenes, and of anthraniloyl-CoA leading to quinoline and acridine alkaloids (see page 377) do not fall into either of the above categories and have now been termed Type TTT PKSs. These enzymes differ from the other examples in that they are homodimeric proteins, they utilize coenzyme A esters rather than acyl carrier proteins, and they employ a single active site to perform a series of decarboxylation, condensation, cyclization, and aromatization reactions. 

These alkaloids occur in the genera Evodia, Hortia, and Zanthoxylum, all members of the Rutaceae, and are restricted to only a few species. Most of the other species in these genera that have been examined yield furoquinoline and acridine alkaloids. Table I is a record of the occurrences, along with empirical formulas and melting points, of the quinazolinocarboline alkaloids. They are all optically inactive except evodiamine, [a]i> +352° (acetone), which is easily racemized. Wuchuyine, C10H13O2N, mp 237°, [a]D — 18°, occurring in E. rutaecarpa (1), evidently... 

Acridine alkaloids Dercitus sp. and Stellatta sp. CHjClz-MeOH H2O (5 5 3) HSCCC... 

There are many additional examples of plant-derived antimalarial agents, most of which are alkaloids. Several acridine alkaloids obtained from members of the family Rutaceae exhibited strong activity against cultured P. yoelii (99), and protoberberine alkaloids (which are widely... 

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