Synthesis and study of biological activity of new tetralone acids analogues of podophyllotoxin

New tetralone acid analogues of podophyllotoxin 7a-c i.e substituted 4-oxo-7-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-6-carboxylic acid were synthesized by Gensler’s method with some changes in reagent and experimental procedure. Substituted 2-(phenyl(thiophen-2-yl)methylene)succinic acids 4a-c were synthesized by stobbe condensation of substituted phenyl(thiophen-2-yl)methanone 2a-c in presence of sodium hydride, diethyl succinate , ethanol in dry benzene to form compounds 3a-c which were subjected into soponification in presence of sodium hydroxide in water and methanol mixture. Compound 4a-c on catalytic hydrogenation in presence palladium over carbon furnished substituted 2-(phenyl(thiophen-2-yl)methyl)succinic acids 5a-c. The compounds 5a-c were refluxed with acetyl chloride to afford benhydril succinic anhydride 6a-c, which on intramolecular cyclisation with Lewis acid like aluminum chloride gave target compounds 7a-c. The structure and products were confirmed by IR, 1H NMR, 13C NMR, mass spectra and elemental analysis data. The synthesized tetralone acids were screened for their antimitotic activity by onion root tip method. The antimitotic activity was compared with control, compounds 7a, 7b, and 7c showed considerable activity. Among the synthesized compounds, 7a exhibited more inhibition compared with remaining synthesized compounds 7b and 7c, at the same time compound 7b showed moderate inhibitions than compound 7c exhibited less inhibitions