Synthesis And Biological Activity Of Dithioacetals

In this work,a new and efficient approach for the chemoselective synthesis of bis(2-hydroxyethyl)dithioacetals using a ZrCl4 as catalyst has been developed.20 bis(2-hydroxyethyl)dithioacetals and 20 new vanillin derivatives containing dithioacetal moiety were designed and synthesized via this method.Their antiviral activities against PVY and CMV were evaluated by using the half-leaf method.Bioassay results demonstrated that some compounds possessed good to excellent activities against potato virus Y(PVY)and cucumber mosaic virus(CMV).The conclusions are shown as follows:1.For the synthesis of bis(2-hydroxyethyl)dithioacetal 3a as an example,the synthesis conditions of the target compounds were selected in different solvents,feed ratio and the amount of catalyst.Finally,the optimum reaction conditions were obtained as following: 1 mol% ZrCl4 as catalyst,under solvent-free condition or THF as solvent,reacts for 5 to 30 minutes at room temperature.With the optimized conditions established,20 bis(2-hydroxyethyl)dithioacetals,14 vanillin derivatives containing bis(2-hydroxyethyl)dithioacetal moiety and 6 vanillin derivatives containing dithioacetal moiety were synthesized,and their structures were fully characterized by 1H NMR,13 C NMR,IR and HRMS.2.A plausible reaction pathway based on experimental results was proposed and verified by results of computational studies.3.The antiviral activities of target compounds against PVY and CMV were evaluated by the half-leaf method using ningnanmycin and ribavirin as controls.Bioassay results demonstrated that target compounds possessed good to excellent activities against potato virus Y(PVY)and cucumber mosaic virus(CMV).Compound 6f containing a bis(2-hydroxyethyl)dithioacetal moiety,exhibited the best curative and protective activities against PVY and CMV in vivo,with 50% effective concentration values of 217.6 ?g/mL,205.7 ?g/m L and 206.3 ?g/m L,186.2 ?g/mL,respectively,better than those of ribavirin(848.0 ?g/mL,808.1 ?g/m L and 858.2 ?g/m L,766.5 ?g/mL,respectively),dufulin(462.6,454.8 ?g/mL and 471.2,465.4 ?g/m L),and ningnanmycin(440.5 ?g/m L,425.3 ?g/m L and 426.1 ?g/m L,405.3 ?g/m L,respectively).