A STRUCTURAL MODIFICATION OF BERBERINE USING CH-ACIDS AND ETHOXYETHYLENES BASED ON THEM

Abstract

Such CH-acids as malononitrile, acetonitrile, and others were shown be effective modifiers of the berberine framework at the C-8 position. Using the example of malononitrile, dimethylbarbituric acid, and Meldrum's acid, it was found that vinyl ethyl ethers obtained by the reaction of the CH-acids and triethyl orthoformate can act as modifiers of the C-13 position. In an alkaline medium, using acetonitrile and malononitrile, both 8-substituted dihydroberberines with an sp³-hybridized C-8 carbon atom and dihydroberberines with an exocyclic double bond at the same atom can be obtained. It was determined that the stability of 13-substituted dihydroberberines depends on the nature of the substituents at the C-8 position and in the vinyl moiety at the C-13 atom. According to molecular docking data, the obtained 8-substituted dihydroberberines with an exocyclic double bond and 13-substituted dihydroberberines are promising for further evaluation in the systemic therapy of oncological diseases.

Authors: Oleg D. Demikhin, Oleg N. Burov*, Mikhail Е. Kletskii, Sergey V. Kurbatov, Elena А. Bereznyak, Alena V. Trishina