Mild and Chemoselective Lactone Ring-Opening with (TMS)ONa. Mechanistic Studies and Application to Sweroside Derivatives

Mild and chemoselective opening of lactones with sodium trimethylsilanolate in high yields and aprotic solvents is described. Kinetic studies demonstrate that the B_Ac2 mechanistic pathway is followed. Nucleophilic attack of silanolate onto the carbonyl of the lactone moiety is the rate-determining step. NaOH present as an impurity accelerates the reaction. The method was further applied to the base-sensitive and stable lactones derived from highly functionalized iridoid derivatives

One-Step Semisynthesis of Oleacein and the Determination as a 5‑Lipoxygenase Inhibitor

The dialdehydes oleacein (<b>2</b>) and oleocanthal (<b>4</b>) are closely related to oleuropein (<b>1</b>) and ligstroside (<b>3</b>), the two latter compounds being abundant iridoids of <i>Olea europaea</i>. By exploiting oleuropein isolated from the plant leaf extract, an efficient procedure has been developed for a one-step semisynthesis of oleacein under Krapcho decarbomethoxylation conditions. Highlighted is the fact that 5-lipoxygenase is a direct target for oleacein with an inhibitory potential (IC₅₀: 2 μM) more potent than oleocanthal (<b>4</b>) and oleuropein (<b>1</b>). This enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes. Taken together, the methodology presented here offers an alternative solution to isolation or total synthesis for the procurement of oleacein, thus facilitating the further development as a potential anti-inflammatory agent