Study of addition of difluorocarbene on double bond of triterpenes

In this work, we describe synthesis and characterization of novel triterpenic derivatives formed by the addition of difluorocarbene on activated double bonds of natural and semisynthetic triterpenes. Despite the general trend that introducing hydrophobicity into the triterpenic molecule often causes decrease in cytotoxic activity, there are examples in literature where addition of dichlorocarbene to a terpenic double bond had the opposite effect. That sparked our interest to synthesize similar analogues from our active triterpenes. The reaction only worked with limited amount of substrates and the cytotoxicity of resulting products was very low. We obtained several interesting structures and the major problem was to accurately determine their structures, especially the configuration at newly introduced chiral carbon atoms. For that, we used 2D-NMR methods combined with molecular modeling and one structure was also confirmed by X-ray crystallography.

We synthesized a group of new compounds formed by the addition of difluorocarbene on activated double bonds of triterpenes. The reaction only worked with limited amount of substrates. We obtained several interesting structures and the major problem was to accurately determine their structures, especially to confirm the configuration at newly introduced chiral carbon atoms. For that, we used advanced 2D-NMR methods combined with molecular modeling and one structure was also confirmed by X-ray crystallography.Figure optionsDownload as PowerPoint slideHighlights
► We synthesized a group of novel difluorocyclopropyl derivatives from natural and semisynthetic triterpenes by adition of difluorocarbenes (generated in situ by heating of sodium chlorodifluoroacetate in diglyme) on CC double bond.
► Only activated double bonds underwent the reactions with difluorocarbene.
► We confirmed the structures of our new difluorocyclopropyl derivatives.
► The configuration on new chiral centers was determined by 2D-NMR techniques and molecular modeling.