Les sécoiridoïdes d’Olea europaea et du Lonicera tatarica : matières premières destinées à la conception de nouveaux synthons chiraux pour la synthèse de composés biologiquement actifs et outils pour le développement de nouvelles méthodes d’extraction et de synthèse

摘要

Secoiridoids are highly functionalized monoterpenes and can be used as renewable raw materials in semi-synthesis when they are abundant in plants. A new green process of water extraction and purification by resins or centrifugal partition chromatography allowed the isolation of more than 100 g of oleuropein from Olea europaea leaves and a dozen of grams of secologanin and sweroside from Lonicera tatarica leaves.The lactone ring opening of perpivaloylsweroside was achieved in apolar solvents by TMSONa. The scope of this reaction was extended to 8 commercial lactones and 5 secoiridoid lactones. A mechanistic approach of this new reaction on γ-butyrolactone was established by kinetic studies. This reaction was used for the conversion of perpivaloylsweroside into secologanin, in four steps. This approach was successfully applied on sweroside derivatives. Four enantiopure secologanin analogs and 9 chiral synthons were isolated. Furthermore the reactivity study of oleuropein afforded 3 new synthons and one isomeric analog of secologanin. These secologanin analogs are synthetic precursors of new indolo-monoterpenic alkaloids. Finally the exocyclic double bond of sweroside was selectively ozonolyzed and epimerized to yield a key synthon for the synthesis of cytotoxic marine diterpenes xenicans.