Furoquinoline

Tandem radical cyclizations of suitably substituted /V-aryl thiocarbamates, thioamides and thioureas have been induced by exposure to 4 equiv. of tnj(trimethylsilyl)silane (TTMSH (TMS)3SiH), 1 equiv. of 2,2 -azo-/h.v-isobu-tyronitrile (AIBN as a radical initiator) and UV light to provide furoquinolines, isofuroquinolines, cyclopentaquinolines, indoloquinolines and related ring systems (Scheme 31).58... 

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. 

Winterfeldt and Nelke have observed the formation of the enamine derivative 35 in the reaction of methyl o-aminophenylacetate (34) with DMAD, which is subsequently cyclized to 3-hydroxy-2-carbomethoxy-methyl-4-carbomethoxyquino e (36), in the presence of sodium methoxide. Acylation of the quinoline derivative (36) leads to a furoquinoline (37) (Scheme 5)/ ... 

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). 

C-2 Chain extension via allylation (578->579) followed by oxidation to expose a latent aldehyde and cyclization constitutes another general route, in this case, leading to skimmianine (580) (Scheme 174) [73JCS(P1)94]. These routes, which overcome problems of poor 3-position reactivity by electrophilic substitution chemistry, were also applied to the furoquinoline... 

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

Bactericidal, Antifungal, and Antibiotic Benzofuran Derivatives Natural griseofulvin and its synthetic derivatives,44 as well as natural and synthetic furoquinolines,45 show such properties, as do some pterocarpans, such as phaseolidin,46 which is antifungal and lipophilic (21). 

Furoquinolines have been obtained by ring closure (H2S04) of o-hydroxylated Bz-allylquinolines (180) (to give, e.g., 2-methyl-2,3-dihydrofuro[2,3-A]quinoline, 181).223 Crotyl ethers give the corresponding 2,3-dimethyl derivatives.233 This method has provided the... 

In the furoquinoline series, Tarbell s technique may also be used 4-acetoxy-l-methyl-3-(l,2-dimethyl-2-propenyl)-2-quinolone (183), obtained by an abnormal Claisen reaction440 and treated with HBr + AcOH at 20° for 26 hours, gives a mixture of the isomeric furoquinolines 184 and 185. 

The method has been extended to o-hydroxyaryl ketones for the synthesis of naphtho[l,2-6]furanes,656 thieno[3,2-e]benzofurans,657 furo-flavones,658 furoxanthones,659 furoquinolines,611,660 phenanthrofur-ans,660 and other complex benzofurans.661... 

Klarman s nietliod779 of dehydrogenation of 2,3-dihydrobenzofurans is achieved with sulfur at 220° (45-85% yields)4,10 or with selenium.214 The method has led to methoxybenzofurans which are difficult to obtain otherwise.10 It has been applied to polycyclic compounds furoquinolines.223,780 naphtho[2,l-5]furan.499... 

Dictamnine (158) on treatment with methyl iodide is converted to isodictamnine (172 sealed tube, 80 °C, 4 h). Other 4-methoxylated furoquinolines show a similar behaviour. These transformations resemble those of a- and y-alkoxyquinolines which on heating with alkyl iodides are converted to A-alkylquinolones. 

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. 

Vilsmeier reaction, 4, 1051 Furo[3,2-6]pyrroles MO calculations, 6, 979 synthesis, 4, 1069 6, 1009 Furo[3,4-a]pyrrolo[2,1,5-cd]indolizine nomenclature, 1, 22 Furopyrylium salts, 4, 993-995 Furoquinolines biosynthesis, 4, 992 occurrence, 4, 988 pharmacology, 4, 992 reactions, 4, 988 synthesis, 4, 989 Furo[3,2-c]quinolines, 4, 991 Furo[3,4-fe]quinoxaline, 1,3-diphenyl-synthesis, 4, 993 Furoquinoxalines, 4, 992 Furo[2,3-6]quinoxalines synthesis, 4, 992 Furosemide toxicity, 1, 136 Furospinulosin UV spectra, 4, 587 Furospongin-I mass spectrometry, 4, 583 Furo[3,4-d][l,2,3]triazole, 2,6-dihydro-synthesis, 6, 996 Furo[3,4 -d][ 1,2,3]triazoles synthesis, 6, 996 Furoxan, 4-amino-3-aryl-tautomerism, 6, 404 Furoxan, 4-amino-3-methyl-synthesis, 4, 414 Furoxan, 4-aryl-3-methyl-rearrangement, 6, 408 Furoxan, 3-aryl-4-nitro-synthesis, 6, 414 Furoxan, 4-benzoyl-3-methyl-oxime... 

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... 

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