Enantioselective Organocatalytic Synthesis of a Secoyohimbane-Inspired Compound Collection with Neuritogenic Activity.

摘要: Natural products provide evolutionary validated core structures inspiring the synthesis of new compound collections endowed with neurite growth-promoting activity. Rhynchophylline is major component Uncaria species which has been used to treat neurological diseases in Chinese traditional medicine. According structure this spirocyclic secoyohimbane alkaloid, we developed a highly enantioselective and efficient organocatalyzed method tetracyclic scaffold incorporating quaternary three tertiary stereogenic centers one-pot multistep reaction sequence. A collection derived secoyohimbanes was synthesized expanded decorating periphery basic additional substituents increase diversity number library members. Evaluation different sub-collections for modulation outgrowth SH-SY5Y human cell line led discovery compounds that promote outgrowth.