Pyrido acridine skeleton

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. 

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. 

Radchenko, O.S., Balaneva, N.N., Denisenko, V.A., and Novikov, V.L. (2006) A simple and effective approach to the synthesis of pyrido [4,3,2-mn]pyrrolo[3,2,l-de]acridine skeleton of amoamines A and B, pentacyclic marine alkaloids from the asddian Cystodytes sp.. Tetrahedron Lett., 47, 7819-7822. 

Among the pyridoacridine alkaloids, meridine 50 and cystodamine 51 exhibit this ring skeleton (see Section II,D,1 on pyrido[2,3,4-k/]acridines). This ring pattern can also be observed in quino[a]acridines 6 and 9 and triquinobenzene 5 (see Section II,A,1 on pyrido[2,3-a]acridines). 

Eilatin 33 and eudistone A 48 and B 49 are pyridoacridine alkaloids that possess this ring skeleton. This ring system is also found in a synthetic isomer, isoascidemin 77, of ascididemin 28 (see pyrido[h]acridines and pyrido[2,3,4-fcf]acridines). Three other alkaloids, the plakinidines (A-C) 78-80 from Plakortis sponge, also share this ring system (90JA1,90TL3271). 

The pentacyclic pyridoacridine alkaloids (amphimedine 105, neoamphi-medine 106, petrosamine 107, and debromopetrosamine 108) also contain this ring skeleton (see pyrido[2,3-4-/c/]acridines). 

Molecules possessing the new skeleton of lH-benzo[c]pyrido[2,3,4-fc/]-acridine 301 with acyl, aminoacyl, and methoxy or aminoalkoxy substituents on the aromatic homocycles were synthesized. Most have therapeutic... 

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