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Alkaloids derived from anthranilic acid undoubtedly
occur in greatest abundance in plants from
the family the Rutaceae. Particularly well represented
are alkaloids based on quinoline and
acridine skeletons (Figure 106). Some quinoline
alkaloids such as quinine and camptothecin have
been established to arise by fundamental rearrangement
of indole systems and have their origins in
tryptophan. A more direct route to
the quinoline ring system is by the combination
of anthranilic acid and acetate/malonate, and an
extension of this process also accounts for the origins
of the acridine ring system (Figure 3.47,
page 81). Thus, anthraniloyl-CoA (Figure 108)
can act as a starter unit for chain extension
via one molecule of malonyl-CoA, and amide formation generates the heterocyclic system, which
will adopt the more stable 4-hydroxy-2-quinolone
form (Figure 108). Position 3 is highly nucleophilic
and susceptible to alkylation, especially
via dimethylallyl diphosphate in the case of these alkaloids. |
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| Figure 108 |
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| Figure 109 |
This allows formation of additional
six- and five-membered oxygen heterocyclic
rings, as seen with other systems, e.g. coumarins,
isoflavonoids, etc. By an
analogous series of reactions, the dimethylallyl derivative can act as a precursor of furoquinoline
alkaloids such as dictamnine and skimmianine(Figure 108). These alkaloids are found
in both Dictamnus albus and Skimmia japonica (Rutaceae). To simplify the mechanistic interpretation
of these reactions, it is more convenient to
consider the di-enol form of the quinolone system.
Should chain extension of anthranilyl-CoA (as
the N-methyl derivative) incorporate three acetate/
malonate units, a polyketide would result
(Figure 109). The acridine skeleton is then produced
by sequential Claisen reaction and C–N linkage<
by an addition reaction, dehydration, and enolization
leading to the stable aromatic tautomer.
Again, the acetate-derived ring, with its alternate
oxygenation, is susceptible to electrophilic attack,
and this can lead to alkylation (with dimethylallyl
diphosphate) or further hydroxylation. Alkaloids melicopicine from Melicope fareana, acronycinefrom Acronychia baueri, and rutacridone from
Ruta graveolens (Rutaceae) typify some of the structural
variety that may then ensue (Figure 109).
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