The scope of thallium nitrate oxidative cyclization of chalcones; synthesis and evaluation of isoflavone and aurone analogs for their inhibitory activity against interleukin-5.

The oxidative cyclization of 2'-hydroxy-6'-cyclohexylmethoxychalcones 5 using thallium (III) nitrate (TTN) in alcoholic solvents produced isoflavones 2 and (or) aurones 3 depending on the electronic nature of p-substituents on ring B. Chalcones with strong electron donating substituents (OH, OCH(3)) were exclusively converted to isoflavones 2. Chalcone with weak electron donating substituents (CH(2)CH(3)) was transformed into isoflavone 2 and the aurone 3 in approximate ratio 1:1. Chalcones with hydrogen or electron withdrawing substituents (Cl, CHO, COOCH(3), and NO(2)) formed aurones 3. Synthesized isoflavones 2 and aurones 3 were evaluated for their inhibitory activity against interleukin-5. Among them, 5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (2h, >100% inhibition at 50 microM, IC(50)=6.1 microM) gave most potent activity. All the aurones 3 were inactive.