Baicalin was identified as a neuraminidase (NA) inhibitor displaying anti-influenza A virus (IAV) activity. However, its poor solubility in saline has limited its use in the clinic. We generated sodium baicalin and showed that it exhibited greatly increased solubility in saline. Its efficacy against oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) was evaluated in vitro and in vivo. Results showed that 10 μM of sodium baicalin inhibited A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and H1N1-H275Y in MDCK cells in a dose-dependent manner, with inhibitory rates of 83.9, 75.9 and 47.7%, respectively. Intravenous administration of sodium baicalin at 100 mg/kg/d enabled the survival of 20% of H1N1-H275Y-infected mice. The treatment alleviated body weight loss and lung injury. Moreover, sodium baicalin exerted a clear inhibitory effect on NAs. The IC values of sodium baicalin against H1N1-H275Y and cells-expressing A/Anhui/1/2013-R294K (H7N9-R294K) NA protein (N9-R294K) were 214.4 μM and 216.3 μM. Direct interactions between sodium baicalin and NA were observed, and we simulated the interactions of sodium baicalin with N9-R294K and N9 near the active sites of OC-N9-R294K and OC-N9. The residues responsible for the sodium baicalin-N9-R294K and sodium baicalin-N9 interactions were the same, confirming that sodium baicalin exerts effects on wild-type and oseltamivir-resistant viral strains.

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Unprecedented Rh­(III)-catalyzed C–H bond difluorovinylation of indoles has been successfully developed, and this method provided an example of direct difluorovinylation reaction through C–H bond activation which was rarely reported. In this context, N-ethoxycarbamoyl served as the directing group and 2,2-difluorovinyl tosylates were used for the construction of difluorovinyl-substituted indoles. This method provided a practical strategy for difluorovinylation of indoles with moderate to good yields and is characterized by the broad synthetic utility, mild conditions, and high efficiency.

An interesting Rh­(III)-catalyzed dual C–H functionalization/cyclization cascade of azomethine imine with diazophosphonate by a removable directing group for the synthesis of highly fused pyrano­[de]­isochromene has been achieved. The transformation shows that the desired pyrano­[de]­isochromenes with two oxygen atoms on its core scaffold could be constructed with good to excellent yields (up to 86%) via a facile one-pot, multiple-step cascade reaction, along with broad generality and versatility.