Studies on quinones. Part 41: synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones.

In the search for new potentially anticancer drugs, isoquinolinequinone-containing polycyclic compounds have been designed and synthesized through highly regiocontrolled cycloaddition reactions of methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate with polarized 1,3-dienes and a thiazole-o-quinodimethane. The new N-heterocyclic quinones were tested on normal human fibroblasts and four distinct human cancer cell lines. Two of the evaluated compounds displayed significant in vitro activity (IC50: 0.

Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones, analogues of kuanoniamine A.

Boc-aminoethylindoloquinone 8, a key intermediate for the building of pentacyclic quinoneimines, analogues of kuanoniamine A, was synthesized by alkylation of 4,7-dimethoxyindole 3 with 1,2-dibromoethane followed by transformation into azide, reduction of the latter with trimethylphosphine in the presence of 2-(tert-butoxycarbonyloximino)-2-phenylacetonitrile and oxydative demethylation of the Boc-amine 6 with silver(II) oxide. Quinone 8 was then treated in situ with the thiazole o-quinodimethane 10 to afford a regioisomeric mixture of the tetracyclic quinones 11. Treatment of the mixture with trifluoroacetic acid and molecular sieves 4-A provided the corresponding quinoneimines 12.

Synthesis and antiprotozoal activity of naphthofuranquinones and naphthothiophenequinones containing a fused thiazole ring.

The synthesis of tetracyclic quinones 10a,b, 14a,b, 19a,b and 20a,b is described. The preparations involve regioselective Diels-Alder reactions via trapping the thiazole o-quinodimethane 9 with several benzofuranquinones and benzothiophenequinones. The structure of the regioisomers was assigned through 2D NMR 1H-13C HMBC experiments performed on 10a and 14a.

Quinonic derivatives active against Toxoplasma gondii.

Quinonic derivatives were tested against a virulent RH strain of Toxoplasma gondii maintained in cell culture in THP-1, a human myelomonocytic cell line. The derivatives were tested at various doses (0.5-4 microg/ml) and compared with the reference molecules clindamycine, sulfadiazine, pyrimethamine and atovaquone.

Generation and Trapping of 4-Methylene-5-(bromomethylene)-4,5-dihydrothiazole with Dienophiles.

4-(Bromomethyl)-5-(dibromomethyl)thiazole (1) was prepared in good yields by bromination of 4,5-dimethylthiazole with 3.3 equiv of NBS in the presence of AIBN. Treatment of 1 with sodium iodide led to a thiazole o-quinodimethane 2 which was trapped in situ with dienophiles such as N-phenylmaleimide, DMAD, or acrylate derivatives.