Acridone alkaloids synthesis

Acridizinium salts, lO-(phenylsuIfonyl)-synthesis, 2, 545 5-Acridone UV spectrum, 2, 156 9-Acridone acylation, 2, 352 alkylation, 2, 350 synthesis, 2, 422 Acridone alkaloids, 2, 513 9-Acridonequinones synthesis, 2, 348 Acridones fluorescence, 2, 20 mass spectrometry, 2, 134 synthesis, 2, 93, 401 from 3-arylanthranils, 2, 496 from benzotriazinones, 2, 506 tautomerism, 2, 347 Acridones, tetrahydro-synthesis... 

Chen, J.-J. Deady, L. W. Mackay, M. F. Synthesis of some acridone alkaloids and related compounds. Tetrahedron 1997, 53, 12717-12728. 

Occurence and New Alkaloids.—Six acridone alkaloids have been isolated from the leaves of Bauerella simplicifolia subsp. neo-scotica. Four of the alkaloids, i.e. melicopine (27), melicopidine (28 R = Me), 1,3-dimethoxy-JV-methylacridone (29 R1 = Me, R2 — H), and xanthovodine (28 R = H), have been obtained from other sources, but the alkaloids (29 R1 = H, R2 = OMe) and (29 R1 — R2 = H) were known previously only as synthetic compounds. The new alkaloids were identified by spectroscopy, by chemical correlation, and by synthesis. 

Acridone alkaloids, experimental antitumor activity of acronycine 21, I (1983) N-Acyliminium ions as intermediates in alkaloid synthesis, 32, 271 (1988) Ajmaline-Sarpagine alkaloids, 8, 789 (1%5), 11, 41 (1968)... 

As part of a general study of the synthesis of 2,2-dimethylpyrano-derivatives, a convenient synthesis of the acridone alkaloid, acronycine (31 R = R = Me) was devised. Heating a solution of 1,3-dihydroxyacridone and 4,4-dimethoxy-2-methylbutan-2-ol in pyridine afforded a mixture of linear and angular pyrano derivatives. The angular product (31 R = R = H), which predominated, is itself a natural compound and was converted by methylation into acronycine. 

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. ... 

Wilson, B.J. (2003) Anionic ortfto-Fries rearrangement of n-carbamoyl diary-lamines, synthesis of the acridone alkaloid junosidine. M.Sc. Thesis. Queen s University, Kingston, Canada. 

Baumert A, Schmidt J, Groger D (1993) Synthesis and mass spectral analysis of coenzyme a thioesters of anthranilic acid and its iV-methyl derivative involved in acridone alkaloid biosynthesis. Phytochem Anal 4 165-170... 

The historical condensation of anthranilic acid (3) with phloroghicinol (206) to give 1,3-dihydroxyacridone (22) by Baczynski and von Niementowdd should be considered as Ae first biomimetic synthesis of an acridone alkaloid (284). The yield of the reaction was initially very poor, but was increased by subsequent modifications by Beck et al. (28S) and by Hlubucek et al. (286). More rec y. Smolders et al. described an efficient condensation of methyl anthranilate (207) with phloroglucinol, in the presence of 4-toluenesulfonic acid in l-hqitanol, which gave 22 in 80% yield (287). 

Dihydroxyacridone prepared in this way has been used fiequently as a starting material for e synthesis of other acridone alkaloids including simple O-and JV-alkylated derivatives (288) and more complex C-prenylanidones (289), pyranoacridones (290,291), and acridone-coumarin mers (292). 

Synthesis of highly oxygenated acridone alkaloids by cyclization of a carboxylic diphenylamine was first introduced by Hughes, Neill and Ritchie for the... 

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. 

The first chapter, by Barbosa-Filho, da-Cunha, and Gray, describes in great detail the tremendous volume of research that has been conducted in recent years on the alkaloids of the Menispermaceae, a family which produces a wide structural range of benzylisoquinoline alkaloids. The second chapter is a very special collaborative effort by three Japanese chemistry groups led by Somei, Murakami, and Ninomiya discussing the recent developments on the synthesis of the ergot alkaloids. Finally, Skaltsounis, Mitaku, and Tillequin discuss the diverse acridone alkaloids from the perspectives of their isolation, distribution, synthesis, and biological properties. 

Synthesis.—Reisch, Mester, and co-workers have made important contributions this year by synthesizing the alkaloids furacridone (34) and ( )-rutacridone (37) for the first time. Regioselective etherification of 1,3-dihydroxy-jV-methylacridone (32 R = H) gave the acetal (33), which furnished furacridone (34) as the major product of acid-catalysed cyclization (Scheme 4). Claisen rearrangements of the 3-allyloxy-acridone (32 R = CH2CH=CH2) and the propargyl derivative (32 R = CH2C=CH) were also studied.18... 

A one-step synthesis of acridones takes advantage of somewhat similar chemistry . Treatment of methyl A-methylanthranilate 570 with lithium A-isopropylcyclohexylamide (LilCA) in THE generated A-lithio salt 571 addition of a halobenzene as the aryne source then produced the acridone 572 as shown, in good yield (40-60%). Substituted haloarenes gave substituted acridones. Utility of the method was demonstrated with a short synthesis of the alkaloid acronyeine 573. 

Full accounts are not available of the synthesis of acridones by the cyclisation, with sodium hydride in dimethyl sulphoxide, of 2-methoxy-benzophenones containing 2 -acetamido- or 2 -methylamino-groups (c/. Vol. 7, p. 90) the alkaloids (41 R = Me) and l,3-dimethoxy-7V-methylacridone have been prepared by this route. ... 

Banderanayake, M., M.J. Begeley, B.O. Brown, D.G. Clarke, L. Crombie, and D.A. Whiting Synthesis of Acridone and Carbazole Alkaloids Involving Pyridine Catalysed Chromene Formation Crystal and Molecular Structure of Dibromocanna-bicyclol and Its Bearing on the Structures of Cyclol Alkaloids. J. Chem. Soc. Perkin I, 999 (1974). 

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 introduction of polyphosphoric acid, instead of phosphoryl chloride, as the reagent for the cyclization of carboxylic diphenylamines permitted the direct access to 9-acridanones, avoiding the tedious steps of acid hydrolysis or alkaline methanolysis of the intermediate 9-chloroacridines (304). This modified process appears as the most popular for the synthesis of simple natural acridones and has been applied to the synthesis of 1,3-dimethoxyacridone (49) (305), 1,3-dimethoxy-lO methylacridone (53) (30S), 1,2,3-trimethoxyacridone (223) (306), 1,2,3-trimethoxy-lO-methylacridone (73) (306), l,2,4-trimethoxy-10-me(iiylacridone (72) (202), l-hydroxy-7-methoxyacridone (46) (307), 1,2,3,5,6-pentamethoxyacridone (95) (210), l-hydroxy-2,3,5,6-tetramethoxyacridone (92) (210), glyfoline (96) (308), and severd congeners of this latter alkaloid (309). 

The key step of the acridone synthesis introduced by Coppola is the condensation of a A methylisatoic anhydride with the lithium enolate of a 2-cyclohexen-l-one. The formed diketo intermediate spontaneously cyclizes into a dihydroacridone, easily aromatized to the corresponding acridone. The versatility of this method, which enables carbon-carbon and carbon-nitrogen bond formation under very mild conditions, is illustrated by the efficient syntheses of the demethoxy analogues of natural fliro and pyranoacridones 319, 320), as well as by those of several naturally occurring alkaloids, including 10-methylacridone (30),... 

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