Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 μM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 μM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 μM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.

General and selective syn-carboxylation-trifluoromethylation of terminal alkynes: application to the late-stage modification of dehydrocholic acid

A general and selective syn-carboxylation-trifluoromethylation across the triple bond of terminal alkynes is developed by virtue of a reactive Cu(iii)–CF3 complex, which produces a broad range of biologically active trifluoromethylated enol esters with excellent regio- and stereoselectivity.