Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin-like Molecules

We report a new synthetic strategy for the flexible preparation of forskolin-like molecules. The approach is different from the previously published works and employs a convergent assembly of the tricyclic labdane-type core from pre-functionalized cyclic building blocks. Stereoselective Michael addition enabled the fragment coupling with excellent control over three newly created contiguous stereocenters, all-carbon quaternary centers included. Silyl enol ether-promoted ring-opening metathesis paired with ring closure were the other key steps enabling concise assembly of the tricyclic core. Late-stage functionalization sequences transformed the tricyclic intermediates into a set of different forskolin-like molecules. The modular nature of the synthetic scheme described herein has the potential to become a general platform for the preparation of analogs of forskolin and other complex tricyclic labdanes.     

The interactions between cholesterol and phospholipids located in the inner leaflet of humane erythrocytes membrane (DPPE and DPPS) in binary and ternary films—The effect of sodium and calcium ions

The studies on the influence of cholesterol on phospholipids accumulated in inner leaflet of membrane are performed rather rarely, especially in the presence of electrolytes, which are present in membrane environment. Therefore, in this work the interactions between cholesterol and saturated phosphatidylethanolamine (PE) and phosphatidylserine (PS) were studied in binary (phospholipid/cholesterol) and ternary (PS/PE/cholesterol) monolayers in the presence and absence of sodium and calcium ions. The composition of ternary films was estimated to reflect the proportion of PSs to PEs in inner layer of human erythrocyte membrane. The influence of electrolytes on pure PS and PE films was also analyzed. It was found that both sodium and calcium ions affect the condensation of DPPS films, and influence the interactions in DPPS/cholesterol monolayers. On the other hand, no effect of these ions on DPPE films as well as on DPPE/cholesterol interactions in the mixed systems was observed. The results obtained for ternary mixtures prove that in the presence of Na⁺ the interactions between the lipids are more favorable than in the absence of these ions. This is in contrast to the effect of Ca²⁺. All the results were thoroughly analyzed in the context of the structure of polar heads of the investigated phospholipids.