10-Methylacridones

In contrast to the case of naphthaldehydes and acetonaphthones, irradiation of the absorption band of 10-methylacridone (AcrCO) results in fluorescence at 413 nm in MeCN [113]. When Sc(OTf)3 is added to an MeCN solution of AcrCO, the absorption bands of 10-methylacridone is red-shifted due to the 1 1 complex... 

Photoaddition of benzyltrimethylsilane with 10-methylacridone (AcrCO) also proceeds via photoinduced electron transfer from PhCH2SiMe3 to AcrCO -Sc(OTf)3 as shown in Scheme 12 [113]. The drastically enhanced... 

Evoxanthine, melicopidine, l,2,3-trimethoxy-10-methylacridone, kokusaginine, evoprenine, evolatine, 1 -hydroxy-2,3-dimethoxy-10-methylacridone, skimmianine, evoxine... 

Alkaloids considered in this section derive biogenetically from 1,3-dihydroxy-lO-methylacridone (19) and 1,3-dihydroxyacridone (22) by simple deoxygenation and/or oxidation of the acridone aromatic skeleton. Subsequent O-alkylation very often takes place, and most natural acridones bear methoxy or methylenedioxy substituents. A few, exemplified by vebilocine (27) (94), evoprenine (28) (95), and 3-graanyloxy-l-hydroxy-4-methoxy-10-methylacridone (29) (96), are also substituted by prenyloxy or geranyloxy groups. 

Deoxygenated products have a restricted distribution. Acridone itself (1) was isolated from Toddalia acukata (97) and Thamnosma montana (98), which also contains 10-methylacridone (30) (99, 100). Alkaloids lacking oxygenated substitution at C-3 include 1-hydroxyacridone, 1,7-dihydroxyacridone, and 1,8-dihydroxyacridone derivatives. It should be noted that 1-methoxy-10-methylacridone (31) and 1,8-dihydroxyacridone (32) were isolated from Samadera aff. bidwillii, the only species of the Simaroubaceae which has afforded this type of secondary metabolite (101). 

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). 

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),... 

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-... 

Selective etherification of the 3-hydroxy group of 1,3-dihydroxy-lO-methyl-acridone (19) with excess bromoacetaldehyde diethylacetal in dry dimethylformamide, either by use of sodium hydride at 120"C in a bomb, or in the presence of potassium carbonate at 100°C under nitrogen, afforded 3-(2,2-diethoxyethoxy)- -hydroxy-10-methylacridone (314). Cyclodehydration of 314 by refluxing in a mixture of dioxane and dilute aqueous sulfuric acid, followed by alkalization by addition of sodium hydroxide and heating, gave the desired furacridone (26), accompanied by smaller amounts of the linear isomer, isofuracridone (315) 330). 

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