Synthesis of Selenoesters via Aldol Condensation and/or Conjugate Reduction and Their Antiviral Activities

A variety of unsaturated selenoesters (including phenolic ones) were produced in good to high yields and with high E/Z ratios using TiCl₄-promoted aldol condensation between Se-phenyl selenoacetate and their respective aldehydes without aqueous workup. A representative phenolic unsaturated selenoester was applied to acylation of tyrosine methyl ester without protection of the phenolic hydroxy groups to furnish the corresponding amino acid conjugate. The conjugate reduction of the unsaturated selenoesters including phenolic ones and selenocoumarin with HSiEt₃ was catalyzed by B(C₆F₅)₃ to afford the corresponding saturated selenoesters in good to high yields. This method was also applicable to the reduction of a saturated selenoester to the corresponding O-silyl hemiselenoacetal in a high yield. Moreover, most acyclic unsaturated selenoesters were found to show good multiple antiviral activities against HIV-1, HBV, and SARS-CoV-2.