Acridine Natural products

Acridines are an important structural feature of many natural products and medicinally important compounds. They can be produced in a straightforward manner by a Friedel-Crafts reaction, the Bernthsen acridine synthesis, 1 9 which couples diaryl amines (such as diphenylamine) with a carboxylic acid (such as benzoic acid) in the presence of a Lewis acid (zinc chloride, ZnCl2, is a typical reagent). Heating to 260°C (10 h) gave a 48% yield of acridine 317.1 9 ... 

K.K. Gruner and H.-J. Knolker (2011) Carbazoles and acridines, in Heterocycles in Natural Product Synthesis, first ed. (eds K.C. Majumdar and S.K. Chattopadhyay), WUey-VCH Verlag GmbH Co. KGaA, pp. 341—376. 

This review summarizes advances in the chemistry of acridines concerning properties, isolation of natural products possessing the acridine ring as a partial structure, new structures of biologically active acridines, and applications of acridines as fluorescent, chemiluminescent, or sensor materials. New synthetic methods for the preparation of acridines mainly published In the last decade as well as new reactions are also reviewed. 

This review summarizes advances in the chemistry of acridines pubfished mainly in the last decade. As more than 1000 pubhcations on acridines appear every year, this review cannot be comprehensive. It presents recent, selected examples of acridines as natural products, as biologically active compounds, some apphcations of technically or biotechnicahy interesting acridines, examples of recendy described syntheses of acridines, and some reactions on the acridine ring. 

Nitrogen heterocycles are especially interesting, since they constitute an important class of natural and nonnatural products, many of which exhibit useful optical properties these have been recently synthesized and evaluated as probes in bioassays purposes 141 —441. Despite the diversity of these compounds, benzoxadiazole, acridone, and acridine fluorophores were chosen as a focus in biolabeling applications. 

A variation in the nature of the reaction products that are formed by the amine reductions of Re3Cl9 is encountered in the case of acridine. The dark green salt (AcrH)2Re3Cl8 is produced rather... 

Coupling reactions of the electrogenerated cation radicals can also occur. If the parent molecule is a good nucleophile, this can be considered as a nucleophilic attack by parent on its own cation radical. The nature of the electrochemical responses in CV and coulometry depend upon whether the coupled product can undergo further oxidation. For example, in the oxidation of aromatic aza-hydrocarbons such as acridine (AcH), studied by Marcoux and Adams (1974), the CV was characterized by an irreversible one-electron wave and coulometry showed an napp-value of one. An analysis of rotating disk voltammograms demonstrated that the reaction sequence (79)-(81) was more probable them that involving... 

Yu et al. [214] investigated a related transformation with anilines in place of ammonium acetate, involving two equivalents of dimedone to afford acridines 126 (Scheme 69). They used a dimeric Bronsted acid IL containing perflu-oroalkyl tails in 1.5 mol% under refluxing condition for 4h to afford acridines in 79-91% yield. The catalytic medium was recycled and reused many times with no appreciable decrease in yield. The electronic nature of substituents present on aromatic aldehydes seldom affected the yield of products however access to acridines was limited to nucleophilic anilines such as para-toluidine and para-anisidine [214]. 

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