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.

Horses in the Early Medieval (10th-13th c.) Religious Rituals of Slavs in Polish Areas-An Archaeozoological, Archaeological and Historical Overview.

Knowledge about horses from early medieval (10th-13th c.) Poland has been largely based on historical and archaeological data. Archaeozoological information has only been used to a limited extent. Therefore, this article aims to present the current state of knowledge on this subject, drawing on archaeozoological data from studies of horse bones. Apart from confirming earlier reflections regarding the sacred significance of the horse, additional information was obtained about specific individuals who were the subject of magical treatments. It turned out that sites with horse skeletons and skulls are few compared to the familiar presence of horse remains among kitchen waste. This contrasts with the neighbouring regions, where horses were buried more frequently among the Germans, Scandinavians and Prussians. Some new data have been obtained thanks to taphonomic analyses, which demonstrated that horse skulls of apotropaic status were not only exposed to public viewing but were also deposited under stronghold ramparts. Horses suffering from infectious diseases could also be buried under such ramparts. Considerations in the article lead to conclusions that horses were used in religious rituals as sacrificial animals, apotropaic deposits, as fortune-telling animals and cosmological figures.

Large-Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N-Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context.

A large-scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N-heterocyclic carbene (NHC) ligand with one 2,5-diisopropylphenyl (DIPP) and one thiophenylmethylene N-substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile of the obtained catalyst was studied in environmentally friendly dimethyl carbonate (DMC). Although VII exhibited low efficiency in cross-metathesis (CM) with electron-deficient partners, good to excellent results were noted for substrates featuring easy to isomerise C-C double bonds. This includes polyfunctional substrates of medicinal chemistry interest, such as analogues of psychoactive 5F-PB-22 and NM-2201 and two PDE5 inhibitors-Sildenafil and Vardenafil. Finally, a larger scale ring-closing metathesis (RCM) of a Vardenafil derivative was conducted in DMC, allowing for straightforward isolation of the expected product (23 g) in high yield and with low Ru contamination level (7.7 ppm).