Functionalization, cyclization and antiviral activity of A-secotriterpenoids

• Novel 2,3-seco-, 1,3-seco- and five-membered ring A triterpenoids were synthesized.
• Cyclizations were achieved by oxonitrile and the Thorpe–Ziegler reactions.
• Intermediates and products were evaluated against HIV-1 and influenza A virus.
• Lupane oximes 5 and 20 exhibit strong inhibitory activity against both viruses.

Triterpene derivatives with an α,β-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses – influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.9–18.2 μM) and HIV-1 (EC50 0.06 μM) were the most promising compounds.

Novel 2,3- and 1,3-secotriterpenoids and five-membered ring A triterpenoids with α,β-alkenenitrile moiety were obtained. Oxime-containing derivatives have a high level of antiviral activity against HIV-1 or influenza A virus.Figure optionsDownload as PowerPoint slide