Synthesis Of DL-epigoitrin Derivatives And Preliminary Evaluation Of Anti-influenza Virus Activity In Vitro

The efficacy studies of Radix Isatidis crude herb and formulations indicate that it has good antiviral activity, in which epigoitrin is regarded for its antiviral active ingredient. In order to study the antiviral mechanism of epigoitrin and research antiviral drugs, we synthesized 18 kinds of derivatives including 8 new compounds by modificating DL-epigoitrin molecular, tested their anti-influenza virus activity in vitro, and discussed their structure-activity relationships.The thesis studies DL-epigoitrin racemate and its derivatives for their chemically synthesis, chiral separation, activity test in vitro and structure-activity relationship. For the synthesis of DL-epigoitrin and its derivatives, we used acrolein as the original material, acted to get 2-trimethylsilanyloxy-3-butenenitrile by cyano nucleophilic addition reaction. Then, it was reducted using lithium aluminum tetrahydrocannabinol to get 1-amino-3-buten-2-ol by deprotection of trimethyl-silyl, and then reacted with carbon disulfide to synthesize DL-epigoitrin racemate by cyclization reaction. At last, some groups were connected to the imino group in DL-epigoitrin racemate by reaction of N-alkylation, N-acylation and N-sulfonylation to get 18 kinds of racemic DL-epigoitrin derivatives including 8 new compounds.Racemic DL-epigoitrin derivatives was initially separated by high performance liquid chromatography (HPLC) using chiral polysaccharide column.11 DL-epigoitrin derivatives were enantioseparated using Chiralpak AD-H column with hexane-ethanol as mobile phase.5 DL-epigoitrin derivatives were enantioseparated using Chiralpak IF column with methanol-water as mobile phase.Anti-influenza virus activity of the racemic DL-epigoitrin and its 18 derivatives were tested in vitro by neuraminidase inhibitors screen. The structure-activity relationships was preliminary discussed according to the test results.