Diels-Alder Reactions between Dienamides and Quinones

• Published in: Chemical & pharmaceutical bulletin Vol. 38; no. 3; p. 688
• Main Authors: CHIGR, Mohamed, FILLION, Houda, ROUGNY, Annie, BERLION, Maryse, RIONDEL, Jacqueline, BERIEL, Helene
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Science and Technology Agency 01.03.1990
• ISSN: 0009-2363; 1347-5223

Tetrahydronapthoquinones and tetrahydroanthraquinones bearing an amido group have been prepared by Diels-Alder reactions between (E)-l-(N-carbobenxyloxyamino)-1, 3-butadiene (2) or (E)-l-(N-benzoyl-N-benzylamino)-1, 3-butadiene (5) and venzoquinone or 5-substituted naphthoquinones. The stereochemistry of the cycloadditions was investigated. A high regioselectivity was observed in the reaction of the diene carbamate 2 with 5-methoxy and 5-acetoxy naphthoquinones. This latter gave the unezpected 1, 8-regioisomer 3d. The cycloadditions of the dienamide 5 with naphthoquinones 1 (R=OH, OMe, OAc) are regiospecific. Assignment of the structure of the tetrahydroanthraquinone 6b is in good agreement with the known directing effect of the 5-hydroxy group of juglone 1b in analogous Diels-Alder reactions. With 5-methoxy and 5-acetoxy naphthoquinones, the opposite regiochemistry observed is consistent with the electron-donating influence of the methoxy or acetoxy group, making the C-3 carbon atom more electron deficient. Aromatization of the adducts 6b and 7c was accompanied by an unusual elimination of the amido moiety. Thus, 1-hydroxy and 1-methoxy anthraquinones were obtained. Reactions of the dienes 2 and 5 with benzoquinone gave the tetrahydronaphthoquinones 9 and 10 with an endo stereospecificity. Oxidation of 9 by activated manganese dioxide gave the naphthoquinone 11. These compounds were submitted to in vitro cytotoxic assays towards murine L 1210 leukemia cells and clonogenic human tumor cell line MDA-MB 231. The naphthoquinone derivatives 9, 10 and 11 had significant activities with IC50[< or =, slant]0.4 μg/ml towards these two tumor cells systems.