Pyridoacridines

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). 

Two new polycyclic pyridoacridine alkaloids, arnoamine B, 289, and its demethylated analogue, arnoamine A, have been isolated from the ascidian Cystodytes sp. These new compounds are the first known examples of pyrroles fused to pyridoacridines, have antifungal properties, and are cytotoxic in several human tumor cell lines <1998JOC1657>. Both these compounds have been synthesized, starting from the hydrazone 290 with a Fischer indole synthesis (Scheme 73) <2000JOC5476>. 

Molinski, T. F. 1993. Marine pyridoacridines alkaloids Structure, synthesis, an biological chemistry. Chemical Reviews, 93 1825-1838. 

Porif.> (hydro)pyrimidine, macroQ clic and oligomeric pyridine or pyridinium, naphthyridine, oxazole, pteridine, pyridoacridine, pyrrole, pyrroloimiiMquinone, (oxa)quinoli2idine, terpenoid indolizidine. ISOPR. Monotero. rare Sesouitem. . Ditero.. Sestertero. also degraded C>i Tritero.. POLYKET. macrolides, polyacetylenes, polycyclic (hydro)quinones, polyethers, (epidioxy)polyp ionates. ... 

Ciufolini, MA. Shm, Y.-C. Bishop, M.J. (1995) A unified strategy for the synthesis of sulfur-containing pyridoacridine alkaloids antitumor agents of marine origin. J. Am. Chem. Soc., 117,12460-9. 

Some 1,7- and 1,8-diazaanthracenediones (e.g., 119) have been used as key intermediates for the synthesis of cytotoxic analogues of the marine pyridoacridine amphimedine 120 <2002BMC2845>. They have also been used in the synthesis of meridine 121 and cystodamine 122 <1998T8421>. 

The methyl sulfide-containing alkaloids, varamines A (123) and B (124) were isolated from L. vareau. Their structures were determined by interpretation of NMR spectral data and by comparison with related alkaloids. The varamines were cytotoxic towards L1210 murine leukaemia cells with IC50 values of 0.03 and 0.05 Xg/mL, respectively [138], The varamines (123-124), lissoclins (110-111) and diplamine (112) all contain a methyl sulfide group linked to a pyridoacridine ring system [22],... 

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]. 

However, pyrroloquinolines and pyridoacridines are the alkaloids of major interest as metabolites in sponges and ascidians [227], Many of these compounds have generated interest both as challenging problems for structure elucidation and synthesis as well as for their cytotoxicities [228-230],... 

As representative of the derivatives of pyridoacridine, eilatin, a marine alkaloid inhibits in vitro cell proliferation in chronic myeloid leukemia patients [244], Other members of the pyridoacridines, such as alkaloids isolated from a Cystodytes sp. ascidian, inhibit topoisomerase II [245], Additionally, analogues derivatives of these type of alkaloids showed interesting anti-HIV activity [246],... 

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. 

The shermilamines constitute a group of alkaloids characterized by a thiazinone ring attached to the pyridoacridine ring system. Shermilamine A (36) was the first known compound of this series and was isolated by Scheuer et al. from the tunicate Trididemnum sp. [38]. The complete... 

Thiazole-containing pyridoacridines are a group of fused ring alkaloids having a pyrido[4,3,2-w, ]thiazolo[3,2-6]acridinium skeleton related to shermilamines, varamines and diplamine, which were discussed in the sulfide section [37]. The pyridoacridines have a characteristic UV absorption pattern [A.max(MeOH) 245, 307, and 361 nm], which is highly sensitive to the pH of the medium. 

Spanish workers have recently described a rapid method for the construction of pyridoacridines which could be of value for the synthesis of a range of cytotoxic pyridoacridine alkaloids. Thus, treatment of MEM-protected 4-quinolone 1 with 3 equivalents of LDA in THF, first at -78°C then with stirring at room temperature, followed by addition of 1 equivalent of methyl 3-formyl-2-pyridinecarboxylate gave, after quench with aqueous ammonium chloride and chromatography, a mixture of the tetracycles 2 (15%) and 3 (20%). Oxidation of either 2 or 3, or a mixture of 2... 

Molinski, T. F., Marine pyridoacridine alkaloids structure, synthesis, and biological chemistry, Chem. Rev., 93, 1825, 1993. 

Ding, Q. Z., Chichak, K., and Lown, J. W., Pyrroloquinoline and pyridoacridine alkaloids from marine sources, Curr. Med. Chem., 6, 1, 1999. 

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. 

Porphobilinogen and Studies of Its Biosynthesis, ft. Neier. Synthesis and Cycloaddition Reactions of Iso-Condensed Heteroaromatic Pyrroles, C. K. Sha. Azacyclopentadienyl Metal Compounds Historical Background and Recent Advances, C. Janiak and N. Kuhn. Recent Developments in the Synthesis of Marine Pyridoacridine Alkaloids, A. M. Echavar-ren. Alkaloid Synthesis Using 1-Acylpyridinium Salts as Intermediates, D. L. Comins and S. P. Joseph. Index. S S... 

Structure, synthesis, and biochemistry of marine pyridoacridine alkaloids 93CRV1825. 

There has been considerable interest in pyridoacridines and related compounds owing to their biological activity (cytotoxicity, mutagenicity, or antibacterial activity). Wawer and coworkers [127] reported the study of a pair of quinoacridinium salts from this... 

Pyridoacridine, Quinoacridine, and Related Alkaloids 461 Tab. 14.9 Che mical shifts of tetrahydrodiazepinopurine analogs of asmarine-A (148) [124],... 

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