Stereoselective synthesis of spirocyclic derivatives of functionalized 2,3,4,7-tetrahydro-1H-azepines

Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes

“…We have explored compounds based on a heterospirocyclic scaffold 8-heterospiro[5.6]dodec-10-ene (Figure 1). The first subseries (oxepenes/oxepanes 1-9) (synthesis (Iusupov, Lukyanenko, et al, 2022) on Scheme S1) contained an oxygen atom in position 8, and azepene subseries 10-15 beared a secondary amine in this position (synthesis (Iusupov & Kurkin, 2024) on Scheme S2).…”

“…We have performed a phenotypic screening of antiviral activity spectrum of fragment-sized (MW ~ 350 Da) small molecules from spiro-annulated oxepane and azepene series (Iusupov & Kurkin, 2024;Iusupov, Lukyanenko, et al, 2022;Iusupov, Lyssenko, et al, 2022) in cell-based assays against several diverse viruses causing human infectious diseases. Antiviral activity was never studied before for these or similar compounds.…”

“…Synthesis of these structures usually relies on the mechanisms involving the ring expansion of either five or six-membered compounds using various methods, for example thermally, photochemically, or by microwave irradiation. In our earlier works a linear sequence of transformations was developed (Iusupov & Kurkin, 2024;Iusupov, Lukyanenko, et al, 2022;Iusupov, Lyssenko, et al, 2022) based on the use of commercially available reagents, which allows to control the process and obtain either spiro-oxepine or spiro-oxepane derivatives. The uniqueness of this chemical transformation is that new spiro derivatives of seven-membered heterocycles with one heteroatom can be obtained in high yield and then can be easily transformed through trivial chemical transformations into further spiro-analogs needed for the structure-activity relationship exploration.…”