3-Quinolone-type alkaloid

Tabernaemontana divaricata (double flower variety) provided an unusual minor alkaloid, voaharine (178), whose structure was established by X-ray analysis [137]. Voaharine is exceptional in being in all probability a tryptamine and jccologanine derived alkaloid but possessing a 3-quinolone instead of an indole chromophore. Voaharine is probably derived from voaphylline (180) (which is also present in the plant) via oxidation and rearrangement and represents the first instance of a 3-quinolone-type alkaloid obtained from Tabernaemontana. Besides these, and the known alkaloids N-methylvoaphylline (181), pachysiphine (tabersonine-P-epoxide) and apparicine, as well as two new bisindoles (vide infra), the plant also provided several new alkaloids of the aspidosperma-type including (-)-mehranine (179), voafinine (182), N-methylvoafinine (183), voafinidine (184) and voalenine (185) which were obtained in minute amounts [138-140]. 

Abe I, Abe T, Wanibuchi K, Noguchi H (2006) Enzymatic formation of quinolone alkaloids by a plant type III polyketide synthase. Org Lett 8 6063-6065... 

The mass spectra of a number of dihydrofuro- and dihydropyrano-4-quinolones had previously been determined,19 but now a survey of sixteen alkaloids of this type has been published.20 Abundant molecular ions are formed from each alkaloid. 

Hydroxy-2-quinolone is a biosynthetic precursor of quinoline alkaloids (see Section VII), and it is not surprising that compounds of this type occur in rutaceous plants (Volume IX, p. 225). Additional 4-methoxy-2-quinolones with or without N-methyl groups have now been reported. 

In a further attempt to produce the Melodinus alkaloid skeleton, 320 was treated with 2 N sulfuric acid at 90-100° for 30 min (183). The product, obtained in 92% yield, was a quinolone, not of the Melodinus type but rather a 3-quinolone having the structure 337. Instead of the... 

Production of both dictamnine (145) and edulinine (151) was stimulated by added 4-hydroxy-2-quinolone (141), a known precursor of furoquinoline alkaloids in intact plants. Subsequent feeding experiments indicated that this precursor (141) was at a branch point for biosynthesis of the two alkaloid types with competitive methylation, which yields (150), causing diversion from furoquinoline to edulinine biosynthesis, a conclusion which may be extendable to whole plants. 

Ptelea trifoliata is the only known source of hemiterpenoid quinoline alkaloids containing terminal double bonds, and nine compounds of this type have been isolated cf. Vols. 1—3, 5, and 7) the synthesis of two members of the group, O-methylptelefolonium iodide (26) and ptelefolone (29), has now been reported (Scheme 4). The 3-prenyl-4-methoxy-2-quinolone (24) was prepared by standard procedures and was converted with a peroxy-acid into a mixture of the dihydropyrano-quinolone (25) and the dihydrofuro-quinolone (27), Treatment of the latter with thionyl chloride and pyridine resulted in regiospecific elimination to give a terminal olefin, which afforded O-methylptelefolonium iodide (26). Successive reaction of the N-methyl-4-quinolone (28) cf. Vol. 7) with triphenyl phosphite dichloride and with pyridine resulted in an efficient synthesis of ptelefolone (29). 

Members of the family contain alkaloids based on several major pathways such as benzylisoquinoline (tyrosine derived), quinolone, furoquinoline, quinazoline (all from anthranilic acid), imidazole (histidine), indoloquinazoline (tryptophan), and both simple aliphatic and aromatic amines. In the tribe Ruteae (Rutoideae), no fewer than five types of alkaloids are common to the three major genera. Quinolone, furoquinoline, and acridone alkaloids are especially widespread within the family, being found in four of the five... 

Further studies with P. citrinum VKM FW-800 obtained from the permafrost region of Northern Russia, led to the isolation of the alkaloids (+)-quinocitrinine A and (—)-quinocitrinine B, which are diastereomers at the C-1 and C-9 stereocenters (186). These alkaloids were the first pyrrolo[3,4-lr]quinoline-type representatives isolated from microbial sources. Their structures are unique in that a quinolone skeleton is conjugated with a y-lactam ring. A biomimetic total S3mthesis of quinolactacin B was reported by Tatsuta s group (215). A new enantioselective synthesis of quinolactacins A2 and B, via the skeletal rearrangement of a p-carboline to the pyrrolo[3,4- ]quinolin-4(lf-D-one system by an... 

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