Study On The Synthesis And Bioactivity Evaluation Of The N-Containing 2(5H)-Furanone Derivatives

The nitrogen atom in the natural products is mainly present as the forms of amides and amines, where the polypeptides, amino acids, mechlorethamines, piperazines, dithiocarbamates and alkaloids are the representative compounds with bioactivity. These organic compounds exhibit good anti-cancer activities, anti-bacterial activities and anti-tumor activities. However, the defects of the weak water-solubility, the strong toxicity and the drug resistance widely exist, which can be accounted by the electronic effect, the coordination effect, the hydrogen bonding, the polarity and the matching degree of the host molecules.This thesis focused on synthesis of the N-containing 2(5H)-furanone derivatives with the characters of low toxicity and excellent bioactivities, which employed the combination of the α,β-unsaturated lactones and the N-containing compounds. The research includes the following four parts:1. Study on the synthesis of chiral 5-alkoxyl-2(5H)-furanones.2. Exploration of the synthesis of chiral 2(5H)-furanones with mechlorethamine as the graft.3. Investigation of the synthesis of chiral 2(5H)-furanones containing dithiocarbamate unit with piperazine as the nitrogen source.4. Study on the synthesis of chiral 2(5H)-furanones containing alkaloid with matrine as the graft.5. Evaluation of the target compounds 7a,7b of human cervical hela cells in vitro inhibitory activity, and compound 7a showed the best inhibition activities with an IC5o of 0.016 μM. Moremover the bioactivity of other compounds are under evaluation now.All the new compounds were confirmed by 1H NMR,13C NMR, IR and HRMS Spectrum.