Acridone ring synthesis

A one-step synthesis of ( )-rutacridone (37) was achieved by the reaction of acridone (32 R = H) with isoprene dibromide isorutacridone (36), the isomer with linear annelation, was a minor product of the reaction (Scheme 5).19 A full account of the synthesis of acronycine from o-aminobenzophenones has now appeared (c/. Vol. 7, p. 90) and a modified route has been described (Scheme 6).20 Cyclization of the benzophenone derivative (38 R = Me) gave acronycine (39) (38%) and isoacronycine (40) (38%) a similar ring-closure of compound (38 R = H) furnished des-iV-methylacronycine. 

Five acridone alkaloids were obtained previously from the bark of Teclea boiviniana cf. Vol. 6, p. 108) a recent investigation showed that the constituents of the leaves are similar, and resulted in the isolation of arborinine (37 R = H), tecleanthine (38 R = H, R = OMe), evoxanthine (38 R = R = H), 6-methoxytecleanthine (38 R = R = OMe), and 1,3,4-trimethoxy-iV-methyl-acridone (39 R = Me, R = OMe). The latter compound has not been obtained previously from a natural source. The n.m.r. and mass spectra indicated that the new alkaloid was a trimethoxy-iV-methylacridone and that ring A was unsubstituted. The three possible acridones had been synthesized earlier, and from melting-point data the alkaloid appeared to be the 1,3,4-trimethoxy-derivative this was confirmed by synthesis using a modification of the published procedures. 1,2,3-Trimethoxy-iV-methylacridone (37 R = Me), previously isolated from Evodia alata, has now been obtained from Melicope leratii. The known alkaloids melicopidine (40 R = Me, R = OMe) and xanthovedine (40 R = R = H) were also shown to be constituents of M. leratii. Arborinine (37 R = H) has been obtained from Vepris pilosa and from Ruta chalapensis. Other known acridone alkaloids isolated from a new source include the l-hydroxy-3-methoxy-deriva-tive (39 R = R = H) and its methyl ether (39 R = Me, R = H), from Vepris pilosa. ... 

D.G. Pintori, M.F. Greaney, Insertion of benzene rings into the amide bond one-step synthesis of acridines and acridones from aryl amides, Org. Lett 12 (2010) 168-171. 

Friedlander Reaction Friedlander condensation is one of the most used and cited reactions in organic synthesis and it is the method of choice for the synthesis of a large variety of nitrogen heterocyclic ring systems such as quinolines, naphthyridines, phenanthrolines, quindolines, or acridones [142]. 

Most methods applicable for the synthesis of a greater vari of simple acridones, including alkaloids bearing numerous oxygenated substituents, also rely on the coupling of two aromatic substrates, which bring the preformed A and C rings of the fiiture acridone skeleton. Thus, closure of the central B lii can be obtained either by cyclization of an intermediate diphenylamine or by cyclization of an intermediate benzophenone. 

The second involves construction of the acridone nucleus in the course of the synthesis. The main approaches used in this latter case are very similar to those which permitted access to the simple acridone alkaloids, e.g. (i) cyclization of a diarylamine intermediate, (ii) cyclization of a benzophenone intermediate, or (iii) construction of the acridone system starting from a quinoline or a quinolinone which bring together the A and B or B and C rings of the acridone skeleton. 

A Cul-catalyzed synthesis of acridones via intramolecular cyclization including C(sp )-H bond activation and C(0)-CHj bond cleavage process using air as the oxidant was reported in 2013 (Scheme 8.100). Many substituents on the aromatic rings are tolerable in the reaction, and the acridin-9(10//)-ones could be obtained in moderate to excellent yields. C-labeling experiments show that only about 86% of carbon atom of carbonyl originates from the substrate. They proposed that a copper-catalyzed intramolecular Friedel-Crafts-type reaction pathway is disfavored [172]. Shortly after the previous report, Fu and coworkers developed a relevant aerobic synthesis of acridone derivatives from l-[2-(arylamino)aryl]ethanones under Cu(02CCF3)2/pyridine/02 catalytic system [173]. 

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