Synthesis of sulfonamide-based amino acid motifs and their inhibition activity against influenza A virus.

The sulfonamide functional group is found in several sulfa drugs and is a very important scaffold in medicinal and synthetic organic chemistry. This paper reports the introduction of the benzenesulfonamide unit into the backbone of unnatural amino acid motifs via C(sp3)-H functionalization and thereby the synthesis of benzenesulfonamide unit-incorporated unnatural amino acid motifs. Benzenesulfonamide unit-incorporated unnatural amino acid motifs were tested for antiviral activity against influenza A virus (IAV), and we identified two hit/lead molecules. Accordingly, high-content screening against IAV identified two lead compounds, 20d-(D) and 20e-(L), which demonstrated good potency in inhibiting IAV infection in A549 cells (a human lung alveolar cell line). We have also screened the utility of the benzenesulfonamide unit-incorporated unnatural amino acid motifs for sensing metal cations.