Dihydrofuroquinolines

LDA metalation of the 2-, 3-, and 4-quinolyl carbamates 401 followed by quenching with propionaldehyde gives respective carbinols 402 which, upon acid-catalyzed cyclization, furnish the dihydrofuroquinolines 336, 403, and 404 (Scheme 125) (88JHC1053). In the case of product 336, this route compares favorably with that based on metalation of 2-ethoxyquino-line (Scheme 102). 

Several further species of Flindersia have been examined for alkaloids and other extractives and the chemistry of this genus has been reviewed (118). The only new alkaloid found was iflflaiamine ([a] n — 0.6° hydrate, mp 62°-63° picrate, mp 207°-209°), the sole alkaloid of the wood of Flindersia ifflaiana F. Muell. (119), which is a dihydrofuroquinoline (XX). Its structure was largely elucidated by spectroscopic measurements. Its UV- and IR-spectra showed it to be a 2-alkoxy-4-quinolone, and the NMR-spectrum showed the presence of three C-methyl groups and one A-methyl (attached to aromatic ring N), a 1,2-disubstituted benzene ring, and other evidence supporting the 2-alkoxy-4-quinolone structure. 

Ethoxyquinoline is lithiated at 3-position. The lithio derivative on reaction with ethylene oxide or allylbromide furnishes the 3-hydroxyethyl or 3-allyl derivatives. These can be readily converted to the dihydrofuroquinolines as shown... 

In the above reactions when the lithio compound is reacted with ethylene oxide, dihydrofuroquinolines are obtained as shown below... 

Data on dihydrofuroquinolines, dihydropyranoquinolines, and related alkaloids are given in Table II (16, 17, 37-60). 

The Haplophyllum alkaloid, khaplofoline (74) (Volume IX, p. 255) (70), is a dimethyldihydropyranoquinolone corresponding to the isopropyl-dihydrofuroquinolines of the type represented by lunasine (63) and lunine (64) haplobucharine (75), the N-prenyl derivative of khaplofoline, has now been isolated from H. bucharicum and its structure has been determined by spectroscopic methods (51). 

This group of alkaloids found in Haplophyllum species can be regarded as hydroxylated derivatives of dihydrofuroquinolines containing terminal double bonds. 

E. Asymmetric Synthesis and Absolute Stereochemistry of Dihydrofuroquinoline and Dihydropyranoquinoline Alkaloids... 

The spectroscopic evidence for the structures of haplophyllidine, per-forine, and perfamine seems convincing, but confirmation is desirable. It would be of particular interest to see whether dehydrogenation of the dihydrofuroquinoline 178 yields an isomer of the alkaloid, foliminine (190). 

Scheme 17. Synthesis of dihydrofuroquinolines by alkylation with ethylene oxide.

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. 

Table 24.4 Occurrence of dihydrofuroquinoline/one alkaloids in Rutaceae species...

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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