IV-Methylacridones

The best-known chemiluminescent acridinium derivative is lucigenin (10,10 -dimethyl-9,9 -biacridinium dinitrate). The reaction with alkahne peroxide produces iV-methylacridone, which emits light at 442 nm. 

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. ... 

Cyclization of a substituted 1 -aiylanthranilamide was the key step for the synthesis of citrusinine-I (76) described by Kato ei al. (312). The required 2-(2-hydroxyphenylamino)-3,4,6-trimethoxy-Af -dimethylbenzamide (235) was obtained by Ullmann reaction of 2-aminophenol with 2-iodo-3,4,6-trimethoxy-iV -dimethylbenzamide (236), prepared in ee steps from commercially available 2,4,S-trimethoxybenzoic acid (237) via o-lithiation of the corresponding amide and subsequent iodination. Benzylation of 235 to 238 was followed by phosphoryl diloride cyclization and hydrolysis of the intermechate with aqueous hydrochloric acid to give 5 benzyloxy-l,3,4-trimethoxyacridone (239) as the major product. Methylation to 5-be izylo3 -l,3,4-trimethoxy-10-methylacridone (240), followed by simultaneous hydrolysis of the benzyloxy group, and of the methoxy group at C-1, gave citrusinine-I I (64). 

Condensation of iV-methylisatoic anhydride (259) with the lithium enolate generated from 2-cyclohexen-l-one (260) gave a P-diketo species which spontaneously cyclized into 1,2-dihydro-lO-methylacridone (261) during the workup process. The dihydroacridone 261 was then quantitatively aromatized to 10-methylacridone (30) in the presence of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone in dichloromethane at room temperature 293). 

Synthesis of 1,2,3-trimethoxy-10-methylacridone (73) and evoxanthine (13) by the same approach necessitated the preparation of 4,5,6-trimethoxy-iV-methyl-isatoic anhydride (262) and 6-methoxy-4,5-methylenedioxy-7V-methylisatoic anhydride (263). Nitration of 2,3,4-trimethoxybenzoic acid (264) afforded 6-nitro-... 

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