Pyridoacridine alkaloids kuanoniamine

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

The pyridoacridine alkaloids, kuanoniamines A-D (133-136) were isolated from an unidentified Micronesian tunicate and its nudibranch predator, Chelynotus semperi. The structures were established by extensive NMR spectral analysis. Cytotoxicity against KB cells ranged from IC50 values >10 ig/mL for kuanoniamine B (134), 5 ig/mL for kuanoniamine D (136), to 1 ig/mL for kuanoniamine A (133) [145]. Kuanoniamine A (133) has also been synthesised [146,147]. 

Gunawardana, G. P., Koehn, F. E., Lee, A. Y., Clardy, J., He, H., and Faulkner, D. J., Pyridoacridine alkaloids from deep-water sponges of the family Pachastrellidae structure revision of dercitin and related compounds and correlation with kuanoniamines, J. Org. Chem., 57, 1523, 1992. 

Pyridoacridine alkaloids have been isolated from sponges ascidians, anemones, and a prosobranch. Two thiazole-containing compounds were obtained, namely kuanoniamine E, 429, and kuanoniamine E, 430 <2002JNP1198>. 

The same strategy has been applied to the preparation of a number of pyridoacridine alkaloids, which include 2-bromoleptoclinidone 29 (90LA205), 11-hydroxyascididemin 30 (93H943) and kuanoniamine A 146 (93H943), and also for the synthesis of neocalliactine acetate 139 (92LA1205 93H943) (a derivative of calliactine 32). 

The pyridoacridine alkaloids isolated from the Micronesian sponge Oceanapia sp. were tested for insecticidal activity, cytotoxicity properties, as well as for their ability to bind to adenosine receptors and to benzodiazepine binding sites of GABAa receptors [91]. Kuanoniamines C... 

Kuanoniamines A-D. The third group of acridine-derived alkaloids to be reported, was the kuanoniamines (35, 36) (Carroll and Scheuer 1990) isolated from a Micronesian tunicate and its prosobranch mollusc predator Chelynotus semperi. Structurally, the kuanoniamines differ from nordercitin and the related compounds discussed above only in the fusion of the thiazole to the pyridoacridine nucleus. Direct proton-carbon shift correlations were... 

---