Alkaloids, furoquinoline

Furoquinoline Alkaloids.—Furoquinoline alkaloids of established constitution have been isolated for the first time from ten species of the Rutaceae (see Table 1,... 

Chen, J.-J., Duh, C.-Y., Huang, H.-Y. and Chen, I.-S. 2003. Furoquinoline alkaloids and cytotoxic constituents from the leaves of Melicope semecarpifolia. Planta Medica, 69 542-546. 

In a series of studies concerning the application of DoM reactions to the synthesis of furoquinoline alkaloids (see Section VIII), Narasimhan and co-workers effected the model metalations of 2-ethoxyquinoline (332) to give, after electrophile quench, low yields of 3-substituted products 335... 

A number of furoquinoline alkaloids are available by taking advantage of in-between metalation of 2,4-dimethoxy quinoline derivatives, as established in model studies (Scheme 103). To illustrate, the trimethoxyquino-line 571, upon metalation and ethylene oxide quench, afforded the carbinol 572 which, upon mild hydrolysis, furnished the alkaloid dihydro-y-fagarine (573) together with the quinolone 574 (Scheme 172) (71T1351). 

Isomeric furoquinoline derivatives 336,403,404 (Scheme 125) related to these alkaloids have been obtained by taking advantage of the powerful carbamate DMG (88JHC1053). 

A number of plants containing furoquinoline alkaloids have been used medicinally, but the alkaloids themselves have found no place in medicine. Skimmianine (159) has been shown to potentiate adrenalin in cats, to relax intestinal muscle, and to raise the tone of striated muscle it has much in common with ephedrine. Dictamnine (158) strongly contracts smooth muscle and stops the isolated frog heart in diastole. Quite recently it has been shown that certain furoquinoline alkaloids are phototoxic to some bacteria and yeasts in long-wavelength UV light (81MI31701). 

The chemistry of thienoquinolines has been explored to a limited degree. Two types (378,379) will be described in this subsection. The pharmacological interest in thieno[2,3-Z>]quinoline (378) and derivatives thereof stems from their isosteric and isoelectronic resemblance to acridine furthermore, (378) constitutes the sulfur analog of furoquinoline (Section 3.17.2.1.5), which is the parent system of a number of alkaloids. Thieno[3,4-6]quinoline (379) is an o-quinonoidal heterocycle which is of interest both for theoretical reasons compared with its isoconjugate analogues and as a synthon in Diels-Alder reactions for the preparation of other condensed heterocycles. 

Al-Rehaily AJ, Ahmad MS, Muhammad I, Al-Thukair AA, Perzanowski HP (2003) Furoquinoline Alkaloids from Teclea nobilis. Phytochemistry 64 1405... 

Furoquinoline Alkaloids.—Glycohaplopine (1 R1 = H, R2 = O-glucosyl, R3 = OMe), a new alkaloid isolated from Haplophyllum perforatum, is believed to contain a /3-glycosidic link.6... 

Prenyl-quinolones and Related Tricyclic Alkaloids.—The l-methyI-3-prenyl-2-quinolone (6 R1 = H, R2 = OMe), already known as a synthetic compound, has been isolated from the roots of Glycosmis mauritiana it is converted into a mixture of the dihydropyrano-quinolones (8 R1 = H, R2 = OMe) and (9 R1 = H, R2 = OMe) by formic acid (Scheme 2).4 A new l-methyl-3-prenyl-2-quinolone, 7V-methylpreskimmianine (6 R1 = R2 = OMe), was obtained from the stem bark of Vepris louisii-, its structure was established by spectroscopy and by its preparation from preskimmianine (7) (Scheme 2).11 A second new alkaloid of Vepris louisii, named veprisine, was shown by spectroscopic studies and by its synthesis from A-methylpreskimmianine to be the pyrano-quinolone (10) (Scheme 2).11 Five furoquinoline alkaloids were found in the wood of Esenbeckia flava (see Table 1) and a non-crystalline bisprenyl compound (11) was also isolated from this source the new alkaloid, which was first obtained as a synthetic compound,17 is readily converted into the dihydropyrano-4-quinolone (9 R1 = R2 = H) (Scheme 2).1... 

From a study of the i.r. spectra of a series of furoquinoline alkaloids containing 4-methoxy-groups, it was concluded that the intensity of ring skeletal vibrations varies with the position of other methoxy-groups and with the nature of the substituents at C-7.17 The conformational mobility of the dihydropyran ring of... 

Furoquinoline Alkaloids.—Well-known furoquinoline alkaloids have been identified for the first time in twelve species of the Rutaceae (see the Table 2.5.8,9,11—13,15,16 on p an(j rare trimethoxydictamnine halfordinine (1 R1 = R2 = R3 = OMe) has been obtained from Araliopsis tabouensis2 and from Teclea verdoorniana.12 The isolation of y-fagarine and skimmianine from Tylophora asthmatica (Asclepiadaceae)14 and skimmianine from Datura stramonium (Solanaceae)4 is of considerable taxonomic interest. 

The three phenolic furoquinoline alkaloids robustine (18), haplopine (1 R = H, R2 = OH, R3 = OMe), and confusameline (1 R1 = R3 = H, R2 = OH), which were synthesized some time ago (see Vols. 3 and 5), have now been prepared by a modification of the Grundon-McCorkindale method, as illustrated for robustine (Scheme 3).22 Polyphosphate ester was found to be more effective than poly-phosphoric acid for cyclization of the alcohol (17) to the dihydrofuran (19). Dehydrogenation to a furoquinoline was accomplished by reaction of the benzyl ether of dihydrofuran (19) with DDQ. 

Platydesmine (5 R = H), the biosynthetic precursor of dictamnine and other furoquinoline alkaloids, has been detected for the first time in a Haplophyllum species H. perforatum).5 Choisya ternata is known to contain O-methyl-balfourodinium salt (4 R = OMe), but now AT-methylplatydesminium salt (4 R = H) has been isolated in equal amount to (4 R = OMe) from the stalks and roots (4 R = OMe) is the predominant quaternary alkaloid of the leaves.3... 

Furoquinoline Alkaloids.—Delbine and montrifoline, the new alkaloids of Monnieria trifolia, were shown by spectroscopic studies to be 4-methoxy-furoquinolines. Delbine is a hydroxy-methoxy-dictamnine, and, as it gives kokusaginine (1 R1 = R2 = OMe, R3 = H) on reaction with diazomethane, the substituents are in positions 6 and 7 since it is not identical with helipavifoline (1 R1 = OMe, R2 = OH, R3 = H) (cf Vol. 7, p. 83), delbine apparently is 6-hydroxy-7-methoxydictamnine (14). Montrifoline was assigned structure (15) on... 

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... 

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]. 

Several note vorthy halogenated terrestrial alkaloids are known, with epibatidine (104) at the top of the list [88]. This apparent frog Epipedobates tricolor) metabolite has powerful analgesic activity [89] and an intensive search is underway for a clinically useful drug [90]. A few chlorinated plant alkaloids have also been discovered. Romucosine F (lOS) is present in Annora purpurea, a South American bushy tree [91], and the closely related romucosine B (106) is found in the stems of RolUnia mucosa [92]. The furoquinoline alkaloid chlorodesnkolbisine (107) was isolated from the African folk medicine plant Teclea nobilis [93]. The authors of this latter study provide convincing evidence that 107 is not an isolation artifact (e.g. from the corresponding epoxide with HCl). 

Dehydrogenation. Dihydrodictamniiie (1) is dehydrogenated to the furoquinoline alkaloid dictamnine (2) in nearly quantitative yield by DDQ in refluxing dioxane... 

A number of simple quinolines and quinolones have been isolated from various rutaceous plants, e.g., from angostura bark (Volume III, p. 80) and from Lunasia amara Blanco (Volume VII, p. 241 this chapter Section IV,A). The leaves of Haplophyllum dubium Eug. Kor (15, 16) contain dubamine (mp 96°-97°) which has been identified (17) as 2-(3,4-methylenedioxyphenyl)quinoline (I). Ruta graveolens L. contains, in addition to furoquinolines, the alkaloids graveoline (mp 205°) (18,19), and graveolinine (mp 115°-116°) (20), the latter (II) is also found in L. amara, and the former is the related l-methyl-4-quinolone (III). 

Such analogies clearly lead to the supposition that the unsubstituted furan ring may arise by the fission of a 3-carbon fragment from the cyclized isopentane unit this idea is far from new in the furocoumarin field 158), but its applicability to the furoquinoline series became obvious only after the structures of alkaloids such as orixine, lunacrine, and balfourodine had been established 14). 

Heliparvifoline. Extracts of H. parvifolia were active against lymphocytic leukaemia and a study of the constituents led to the isolation of a new furoquinoline, helipar-vifoline. The alkaloid was shown to be either 7-hydroxy-6-methoxydictamnine (7)... 

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