Furanoquinoline alkaloids

In the oxazole-containing species recognized thus far, anthranilate is evidently not always shunted into nicotinate formation as some of these taxa accumulate products attributable to a more direct utilization of anthranilate. Halfordia ken-dack contains the quinoline alkaloid halfordamine (55) and the furanoquinoline halfordinine (56) (8, 22), while small quantities of dictamnine (57) occur in H. 

A general synthetic procedure to alkaloids of this type, as well as to furanoquinoline structures, has been announced (M. Ramesh, P.S. Mohan and P. Shanmugan, Tetrahedron, 1984, 40, 4041 see also p.3431 ). The versatility of this approach is illustrated by syntheses of atanine, flindersine, orcine, preskimmianine, 0-methylglycosolone and zanthobungeanine. 

Quinoline and Acridone Alkaloids.—Earlier studies have shown that the quinoline nucleus of skimmianine (38) and dictamnine (37) is derived from anthranilic acid and acetate. Whilst incorporation of mevalonate into dictamnine in Dictamnus albus and into the furanoquinoline alkaloids of Skirnmia japonica could not be demonstrated, positive results have been obtained in Fagara coco. [4- " C]Mevalonic acid, [5- " C]mevalonic acid, and [l- " C]dimethylallyl alcohol were satisfactorily incorporated into skimmianine (38) and the activity was confined essentially to C-2, C-3, and C-3 respectively. 

The above results strongly suggest that in the biological formation of the furanoquinoline alkaloids an isoprene unit (probably as isopentenyl pyrophosphate) is introduced into 2,4-dihydroxyquinoline to give (35). Cyclisation of this intermediate leads to isopropylidene-furanoquinolines e.g. platydesminium salt (36). Then elimination of the side chain gives the dictamnine (37) type. 

The biosynthesis is closely related to the already established route to the quinoline system of the furanoquinoline alkaloids such as skimmianine (107) (Scheme 25). Two papers have been published this year on the biosynthesis of (107) but they add nothing new to the earlier work reviewed last year.73 Briefly, the results confirm that (i) C(2) and C(3) of the furan ring of (107) are derived in Fagara coco plants from C(4) and C(5) respectively of mevalonic acid,74 (ii) in the same plant, activity is incorporated specifically at C(3) of the furan from C(l) of dimethylallyl alcohol,75 and (iff) 2,4-dihydroxy[3-14C,15N]quinoline (106) is an efficient and specific precursor of the quinoline system of (107) in Ruta graveolens and is incorporated without randomization.75 Surprisingly, the isomer kokusaginine (108) showed a random incorporation in this experiment. 

D. oreophila contain N,N-dimethyl-5-methoxytryptamine, 2-methyl-6-methoxy-l,2,3,4-tetrahydro-6-carboline, together with hordenine and kokusaginine, and the stem bark contains kokusaginine and three other furanoquinoline bases. The leaves of D. drupacea yielded N,N-dimethyl-5-methoxytryptamine again the stem bark contained only quinoline alkaloids. 

Rutae herba can be characterized by its coumarins (e.g. rutamarin), the furano-coumarins (e.g. bergapten, psoralen) as well as the furanoquinoline alkaloids (e.g, kokusagine, Y-fagarine) and the flavonol glycoside rutin. 

The lipophilic coumarins and furanoquinolin alkaloids (T2/T3) migrate in one blue fluorescent major zone up to the solvent front. 

Quinoline Alkaloids.—An efficient and specific conversion of (-f)-platydesmine (156), C-labelled as shown, into dictamnine (157) has been demonstrated in Skimmia japonica, as has its presence in this plant. Its role as an intermediate between the dimethylallylquinoline (155) and the furanoquinoline dictamnine is thus established. Platydesmine was also incorporated into platydesminium metho-salt (159) and skimmianine (158), but into the latter with low efficiency. The metho-salt (159) was poorly incorporated into dictamnine. 

The formation of benzofuranoid and analogous ring systems seems to follow a common pathway. In the rotenoid amorphigenin (25) the sequence is shown in Scheme 3. Here all five carbon atoms are retained. With the furanocoumarins there is a loss of three carbon atoms but the initial stages are probably analogous. Several studies on these sequences are summarized in Scheme 4. A similar process occurs in the biosynthesis of furanoquinoline alkaloids (see Scheme 5). 

Rutaceae alkaloids aUetdoids from common rue Rusa graveolens L.) and other members of the Rutaceae. They include quinoline, furanoquinoline, pyra-noquinoline and acridine compounds, all biosynthesized from anthranilic add. The furanoquinolines have spasmolytic activity, and the drugs are sometimes used therapeutically. 

The bases isolated from plants of the genus Lunasia (Rutaceae) also belong to the furanoquinoline alkaloids. Ruegger and Staufeacheb... 

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