No abstract

Molecular rearrangment of rastevione mesylate {!] in alkaline medium afforded two epimeric 2,6,6,11 -tetramethyltricyclo[5.4.0.04,8]undecane derivatives [2 and 3] by a 1,3-bond migration. Their stereostructures, which possess a new hydrocarbon skeleton named arteagane, were elucidated from nmr data in combination with X-ray diffraction analyses of 3 and its diacetate 7. The conformations of 2, 3, and several derivatives are reported.Molecular rearrangements of natural products offer the possibility of generating substances with novel skeletons (1-3) and increased understanding of their chemical behavior (4-6), which can be applied to synthetic approaches (7,8). In continuation of our research on molecular rearrangements of sesquiterpenes (9,10), we report herein the transformation of the longi^inene derivative rastevione mesylate [1] to the 2,6,6,11tetramethyltricyclo[5.4.0.0 ' Jundecane derivatives 2 and 3 by a 1,3-bond migration.

Fourteen coumarin-derived compounds modified at the C3 carbon of coumarin with an α,β-unsaturated ketone were synthesized. These compounds may be designated as chalcocoumarins (3-cinnamoyl-2H-chromen-2-ones). Both chalcones and coumarins are recognized scaffolds in medicinal chemistry, showing diverse biological and pharmacological properties among which neuroprotective activities and multiple enzyme inhibition, including mitochondrial enzyme systems, stand out. The evaluation of monoamine oxidase B (MAO-B) inhibitors has aroused considerable interest as therapeutic agents for neurodegenerative diseases such as Parkinson’s. Of the fourteen chalcocumarins evaluated here against MAO-B, ChC4 showed the strongest activity in vitro, with IC50 = 0.76 ± 0.08 µM. Computational docking, molecular dynamics and MM/GBSA studies, confirm that ChC4 binds very stably to the active rMAO-B site, explaining the experimental inhibition data.

Eleven new substances related to the proposed mechanistic pathway from longipinane 2 to arteagane (2,6,6,11-tetramethyltricyclo[5.4.0.04,8]undecane) derivatives were prepared and are discussed.