Furanoquinoline

The ionic liquid [bmim][BF ] is known to catalyze the aza-Diels-Alder reaction in the synthesis of pyrano- and furanoquinolines [190]. This reaction was also catalyzed by the enantiopure bis-imidazolinium salt 67 in 67% yield with an endo. exo ratio of 60 40 (Scheme 69) [191]. The product was obtained as a race-mate. In addition the aza-Diels-Alder reaction with imines and Danishefsky s diene was catalyzed by the salt 67 giving racemic product. The salt and its analogues could be easily prepared via the oxidation of the corresponding aminals [192]. Investigation of the influence of the counter anion in achiral C2-substituted imidazolinium salts, which can be also described as 4,5-dihydroimidazolium or saturated imidazolium salts, in the aza-Diels-Alder reaction showed, that the catalytic activity increased, the more lipophilic the counter anion and therefore the more hydrophobic the salt was [193]. 

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. 

Furanocoumarin and Furanoquinoline Derivatives.—The two extra carbon atoms of these furanoid rings are derived from C 4,5 of mevalonic acid. Probably very similar processes occur in both types of secondary metabolites. For ex-ample, psoralen (21 R = H) and bergapten (21 R = OH) are derived from umbelliferone (18) via marmesin (19) and their dihydro-derivatives (20). An... 

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). 

Yadav has demonstrated another aza-Diels-Alder reaction in the formation of pyrano- and furanoquinolines from anilines, aldehydes and dihydropyran or di-hydrofuran in ionic liquids such as [BMIM][BF4] [185]. The reaction involves the... 

Towers, G.H.N. Abramosky, Z. 1983. UV-mediated genotox-icity of furanoquinoline and of certain tryptophan-derived MsaXmds. Journal of Natural Products Vol. 46 576-581. 

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. 

In some cases the coumarins formed may be further hydroxylated, methylated or substituted by isopentenyl residues. Furanocoumarins, e.g., pimpinellin, psoralen and xanthotoxin (Fig. 298), and dihydropyranocoumarins, e.g., braylin, derive from isoprenylated coumarins. The additional furane ring may be formed by the series of reactions outlined for furanoquinolines (D 8.4.2). 

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

Towers GHN, Graham EA, Spenser ID, Abromowski Z (1981) Phototoxic furanoquinolines of the Rutaceae. Planta Med 41 136-142... 

In this protocol, nano-silica chromic add (nano-SCA) is found to catalyze efficiently the three-component coupling reactions of aldehydes, amines, and cyclic enol ethers such as 3,4-dihydro-2//-pyian and 2,3-dihydrofuran under mild conditions to afford the corresponding pyrano- and furanoquinolines in excellent yields with high endo-selectivity. 

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