Furoquinolin-4-ones

Dictamnine (7, R = Me) was a specific precursor of skimmianine (7, R = Me, 7,8-diOMe) and other furoquinoline alkaloids oxygenate in the aromatic ring in Skimmia japonica and Choisya ternate [41] similar results were obtained with cell cultures of Ruta graveolens [104]. Dihydro- (5) and furoquinolin-4-ones (8) are also known. 

Table 24.5 Occurrence of furoquinolin/one alkaloids in Rutaceae species... 

Dimethyl-3 -hydroxydihydropyranoquinolin/4-ones (10, 11) have been obtained from several rutaceous species. Although tracer feeding experiments have not been reported, the co-occurrence of furoquinolin/one and these pyrano derivatives suggest that the biosynthesis of both groups involve oxidative cyclization of a common 3-(2,3-epoxy-3-methybutenyl)-4-hydroxyquinolin-2-one precursor. 

DNA can also be a target for alkaloids planar and lipophilic alkaloids, such as berberine and sanguinarine (Figure 1.6) are intercalating compounds that assemble between the stacks of paired nucleotides in the DNA double helix [2,3,18,23]. DNA intercalation can disturb replication, DNA repair, and DNA topoisomerases. Frameshift mutations are one of the adverse consequences of intercalating compounds. Some alkaloids, such as pyrrolizidine alkaloids, aristolochic acids, cycasin, and furoquinoline alkaloids, are known to form covalent adducts with DNA bases. Mutations and tumor formation can be the result of such interactions. DNA alkylation occurs in some alkaloids only after activation by liver enzymes, such as cytochrome p450 oxidases (pyrrolizidine alkaloids, aristolochic acids) [17,18,24]. 

Alkoxyl radicals can easily be generated photochemically from hypobromites and hypoiodites and have a variety of synthetic uses. j8-Cleavage of the alkoxyl radical is involved in many of these transformations. An efficient synthesis of 5,7-dihydroxy-4-methyl-isobenzofuran-1 (3ff)-one has been achieved in this way, and jS-scission of the cyclobutanoxyl radicals, derived from [ 2 + w2] photoadducts of 4-hydroxyquinol-2-one and alkenes, affords furoquinolines. Regioselective 8-scission has been observed in... 

The family Rutaceae was one of the first to be examined as a result of the systematic alkaloid investigations launched by the CS1RO, and complemented by studies undertaken in several Australian universities. The family was already known to produce furoquinoline... 

The occurrence of new furoquinoline alkaloids and their physical properties are indicated in Table VII. N-Methyl-4-quinolones, the so-called isoalkaloids are well known one example is isodictamnine (164), obtained by heating dictamnine with methyl iodide. Isodictamnine, iso-pteleine, isomaculosidine, and isoflindersiamine have now been recognized as constituents of rutaceous species the N-isopentyl alkaloids of Acronychia are also in this category. The alkaloids discussed in this section are grouped in accord with the pattern of oxygenation in the aromatic ring. 

It is worth noting that one C-N, one C-O, and three C-C bonds were formed with the concomitant creation of five asymmetric centers in this one-pot process. The oxazole 65 could be isolated if the reaction was performed at rt Significantly, the same reaction using ortHo-aminophenyl propiolate 67 instead of 64 in the presence of ammonium chloride furnished furoquinoline 69 in 75% yield (Eq. (2), Scheme 15.22) [39]. The intramolecular DA cycloaddition of 68 followed by retro DA and oxidation accounted for the formation of 69. These two examples demonstrated how subtle structural modification of one input (64 vs 67) in a given MCR could diversify the structure of the reaction product Compound 66 is a product with up to five stereocenters, while 69 is a flat aromatic heterocycle. 

Quinoline and Furoquinoline Alkaloids (Fig. 151). (Activated ) anthranilic acid reacts with (activated ) acetic acid to 2,4-dihydroxyquinoline. Probably 2-aminobenzoyl acetic acid, which is in a pH-dependent equilibrium with 2,4-dihydroxy quinoline, or an activated derivative of this compound is an intermediate. On the one hand 2,4-dihydroxy quinoline is transformed to echinorine. On the other hand it is a precursor of 3-prenylated chinoline alkaloids, isopropyl-dihydrofuroquinolines and furoquinolines. 

The anellation of the three-ring system is generally linear, such as in dictamnine (7, R = Me), but a few representatives with angular anellation have been found, e.g., 2, 3 -dihydrofuroquinolin-2-one araliopsine (9, N-Me) isolated from Araliopsis soyauxii [44], However, angular furoquinoline alkaloids are not known. 

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