Pyranoquinoline alkaloids

Reaction of 4-hydroxyquinoline-2-one 598 with oxalyl chloride gave oxazoloquinoline 599 (970PP211). The oxazoloquinoline 600 was obtained as a byproduct during the synthesis of pyranoquinoline alkaloids 601 by reaction of 598 with 2-methyl-2-chlorobutyne under phase transfer catalysis (87JHC869) (Scheme 101). 

The angular isomer on treatment with CHjMgl gives flindersine 99, a pyranoquinoline alkaloid... 

Ribalinidine and ribaline were also obtained from Ruta graveolens (53). This species contains the quaternary rutalinium salt (46), corresponding to ribalinidine (43). Rutalinium, the first example of a quaternary salt in the pyranoquinoline series of alkaloids, was converted into the tertiary base en heating in pyridine (53). 

The assignment of configurations supports the mechanisms proposed for some well-known reactions of furo- and pyranoquinoline alkaloids. Thus, balfourolone (103) is believed to be an artifact formed from 0-methyI-balfourodinium salt with aqueous base, and the (I ) configurations of both compounds are consistent with a mechanism involving nucleophilic reaction at the 2-position of the quinoline ring. Conversion of (—)-(K)-balfourolone (103) into (+)-( )-isobalfourodine (104) with aqueous acid occurs at the tertiary center without affecting the chiral center, as expected. 

Pyranoquinoline alkaloids are another important group of quinoline derivatives that possess strong biological activities, from potent inhibitors of platelet aggregation such as zanthodioline, to cytotoxic compounds acting selectively to breast cancer cells such as huajiaosimuline."... 

Many quinolone alkaloids are subject to prenylation and give rise to the furoquinoline or pyranoquinoline alkaloids. The furan rings of furoquinoline alkaloids arise by a similar process to thos of furanocoumarins that have been previously discussed (Fig. 31.8). see also Chapter 9) (Geissman and Crout, 1969 Grundon, 1979, 1983). 

Fig. 31.6. Quinoline, fiiroquinoline, and pyranoquinoline alkaloids (modified from Geissman and Grout, 1969).

Furoquinoline and pyranoquinoline alkaloids primarily are known from the Rutaceae and occur in four of the five alkaloid-containing subfamilies (Aurantioideae, Flindersi-oideae, Rutoideae, and Toddalioideae). The most common is skimmianine (15) (Grundon, 1979). 

Pyranoquinoline alkaloids, such as ribalinine (20) and isobalfourodine (21), appear to arise from the same epoxide intermediate involved in the formation of furoquinoline alkaloids. However, differences in stereochemistry of the prod-... 

Table 24.8 Occurrence of linear dihydro-, pyranoqumoline/4(l//)-one and angular dihydro-, pyranoquinolin-2(l//)-one alkaloids in Rutaceae species ...

Angular pyranoquinolin-2(l//)-one are more widely distributed in the mtaceous species, however, the possible precursor angular 2, 2 -dimethyl-3 -hydroxydihydropyranoquinolin-2-one had not been reported until 2006. Thus, Grundon suggested that these alkaloids might be biogenetically derived from an alternative mechanism involving a quinone methide intermediate, as illustrated by a synthesis of A-methylflindersine in Scheme 24.3 [112]. 

More recently, angular 2, 2 -dimethyl-3 -hydroxydihydropyranoquinolin-2-one (15) was isolated from Skimmia laureolea [69], which provided substantial indirect evidence that the loss of the hydroxyl substituent at C-3 may be involved in the formation of pyranoquinolin-2-one (16, Scheme 24.1). This probably represents the natural process for all pyrano rings in quinoline alkaloids. 

Synthesis of TetrahydroquinoUne Alkaloids The pyranoquinoline core stmcture is the... 

The pyranoquinoline moiety is an important stractural feature of many alkaloids isolated from Rutaceae family [42] for example, flindersine, oricine, and verprisine [43] which have attracted great attention of synthetic as well as medicinal chemists. 

Pyranoquinoline alkaloids simulenoline 84 [51,52] and hua-jiaosimuline 85 [53] were isolated from root barks of... 

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