Synthesis Of New Chiral Gamma-Alkoxy-2(5h)-Furanone-Piperazine-Sulfonamide Compounds And Preliminary Evaluation Of In Vitro Anticancer Activity

The enantiomerically pure 5-(S)-5-alkoxy-3,4-dibromo-2(5H)-furanones were readily prepared from furfural through a three-step sequence of bromine-promoted oxidation/acetalization of mucobromic acid with chiral (-)-menthol and (+)-borneol/recrystallization of the resulting gamma-butenolides. Then the chiral gamma-butenolides were reacted with piperazine through a one-pot two-step protocol combining Michael addition and elimination of hydrogen bromide, resulting in the crude furanone-piperazines. which were further toslated with a range of sulfonyl chlorides. 12 furanone-piperazine-sulfonamide complexs were efficiently obtained in moderate to excellent yields (45.3%similar to 96.2%). All the new compounds were identified by H-1 NMR, C-13 NMR, IR and HRMS technology. The in vitro anti-tumor activities of these complexs against cervical cancer cell lines (Hela) were evaluated by thiazolylblue (MTT) assay method. Among them, 5-(S)-5-borneolyloxy-4-(p-nitrobenzenesulfonamide-piPeraziny1)-3-bromo-2(5H)-furanone (7k) exhibited the best inhibitory activity with an IC50 of 0.02 mu mol/L, providing a new promising lead for further development of new anti-Hela drugs.