MODIFIED HETEROAROTINOIDS AS POTENTIAL ANTICANCER AGENTS—IMPROVED SYNTHESES OF 2-NITROTETRALIN AND 2-AMINOTETRALIN

A series of modified heteroarotinoids were prepared. Methods to obtain systems with closed ring units and with open chains have been developed. Heteroarotinoids with a thiourea or urea linking group between two aryl rings comprise the major structures. A group of amino-substituted arenes were condensed with 4- nitrophenylisocyanate or 4-nitrophenylisothiocyanate in extremely dry THF under N2 at 0 ˚C, the resulting mixtures being left a room temperature with stirring for 24 h. Flash chromatography or one simple recrystallization afforded solids with an average yield of 65.5% for 16 compounds. Both spectral and elemental analysis supported each structure. Synthetic methodology to obtain somewhat rare intermediates 2-nitrotetralin and 2-aminotetralin in a consistent manner are reported. The modified heteroarotinoids have potential as agents to treat ovarian cancer.