Pyrido acridines

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

Koren-Goldschlager, G., Aknin, M., and Kashman, Y. (2000) Cycloshermilamine D, a new pyrido-acridine from the marine tunicate Cystodytes violatinctus. J. Nat. Prod., 63,830-831. 

Plubrukam, A. and Davidson, B.S. (1998) Amoamines A and B, new cytotoxic pentacydic pyrido-acridine alkaloids from the ascidian Cystodytes sp. J. Org. Chem., 63,1657-1659. 

The thermal cyclization of 3-acridinylaminomethylenemalonates (921) by heating in diphenyl ether at 260-270°C for 20 min afforded pyrido[2, 3-c]acridine-2-carboxylates (922) in good yields [77JAP(K)3099, 77USP 4060527]. 

Heterocyclic compounds which have, as a common structural feature, a tetracyclic pyrido[2,3,4-k/ acridine system often offer striking biological activities such as antitumor activities. Specifically, a facile synthesis of ascididemine (70) was achieved by high-pressure IEDAR of 6H-4-bromopyrido[2,3,4-/d]acridin-6-one (69) with propanal dimethylhydrazone... 

Synthesis of 7//-pyrido[2,3,4-/c/]acridines related to marine alkaloids 92H(34)2385. 

A new synthesis was developed by Y. Kashman et al. for the preparation of the parent pyrido[2,3,4-/c/]acridine skeleton utilizing the Doebner-Miller synthesis. In the first step, 3-aminoacetanilide was reacted with vinyl phenyl ketone in the presence of m-nitrobenzenesulfonic acid sodium salt and acetic acid to afford the corresponding 4-phenylquinolines. The acetamide group was then converted to the corresponding aryl azide, which underwent intramolecular nitrene insertion upon thermolysis to give the desired heterocyclic skeleton. 

Gellerman, G., Rudi, A., Kashman, Y. Synthesis of pyrido[2,3,4-kl]acridines. A building block for the synthesis of pyridoacridine alkaloids. Tetrahedron Lett. 1992, 33, 5577-5580. 

Depending on the ring fusion, pyridoacridines can be classified into the following main classes pyrido[a]acridines (benzo[ ]phenanthrolines), pyrido[b]acridines, pyrido[c]acridines (benzo[h]phenanthrolines), and pyr-ido[k/]acridines (dibenzo[/,i/][2,7]naphthyridines). 

The pyridine ring is fused at bond a of the acridine. Depending on the position of the nitrogen in the fused pyridine ring, four different types of pyrido[fl]acridines are possible. 

In an attempted reaction toward a pyrido[2,3,4-/c/]acridine, Gellerman et al. (92TL5577) isolated a pyrido[2,3-a]acridine 11 from an acid-catalyzed reaction between l-amino-4-methylacridin-9(10//)one 10 and acetylace-tone (Scheme 4). 

We have prepared pyrido[3,2-fl]acridines, 20 and 21 (96TH1), by Lewis acid-catalyzed cyclization of enamines 18, formed by the condensation of... 

The synthesis of some hexa- and heptacyclic molecules 24 and 25 containing a pyrido[3,2-fl]acridine nucleus has been reported, the principal step being the ring closure of anthraquinone-derived precursors 22 and 23 (Scheme 6) (84KGS962). 

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