Synthesis

NSPD-12m was synthesized using the Knoevenagel condensation reactions as previously described (He et al., 2013). Briefly, a mixture of an aldehyde compound N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethyl-3-formylpyrrole and a rhodanine derivative 3-(2-(trifluoromethyl)benzyl)-2-thioxothiazolidin-4-one (mole ratio 1:1) in the presence of ammonium acetate (100 mg) in toluene (20 ml/mM) and methanol (10 ml/mM) was heated to reflux for 3–5 h. After the reaction was finished, ethyl acetate was added to the solution. Water and brine were used to wash the organic phase, successively. After drying over anhydrous sodium sulfate and removing the solvent under reduced pressure, the residue was purified by a flash silica column [gradual eluent: ethyl acetate/petroleum ether with acetic acid (3%), 0–60%] to yield the pure product.