1440705-33-8Relevant academic research and scientific papers
Enantioselective Organocatalytic Synthesis of a Secoyohimbane-Inspired Compound Collection with Neuritogenic Activity
F?rster, Tim,López-Tosco, Sara,Ziegler, Slava,Antonchick, Andrey P.,Waldmann, Herbert
, p. 1098 - 1108 (2017)
Natural products provide evolutionary validated core structures to inspire the synthesis of new compound collections endowed with neurite growth-promoting activity. Rhynchophylline is the major component of Uncaria species, and has been used to treat neurological diseases in Chinese traditional medicine. Based on the structure of this spirocyclic secoyohimbane alkaloid, we developed a highly enantioselective and efficient organocatalyzed synthesis method to provide a tetracyclic secoyohimbane scaffold incorporating a quaternary and three tertiary stereogenic centers, in a one-pot multistep reaction sequence. A compound collection of derived secoyohimbanes was synthesized and expanded by decorating the periphery of the basic scaffold with additional substituents to increase the diversity. Evaluation of the different subcollections of secoyohimbanes for modulation of neurite outgrowth in the SH-SY5Y human cell line led to the discovery of new compounds that promote neurite outgrowth.
Highly enantioselective catalytic synthesis of neurite growth-promoting secoyohimbanes
Antonchick, Andrey P.,Lopez-Tosco, Sara,Parga, Juan,Sievers, Sonja,Schuermann, Markus,Preut, Hans,Hoeing, Susanne,Schoeler, Hans R.,Sterneckert, Jared,Rauh, Daniel,Waldmann, Herbert
, p. 500 - 509 (2013/06/27)
Natural products endowed with neuromodulatory activity and their underlying structural scaffolds may inspire the synthesis of novel neurotrophic compound classes. The spirocyclic secoyohimbane alkaloid rhynchophylline is the major component of the extracts of Uncaria species used in Chinese traditional medicine for treatment of disorders of the central nervous system. Based on the structure of rhynchophylline, a highly enantioselective and efficient organocatalyzed synthesis method was developed that gives access to the tetracyclic secoyohimbane scaffold, embodying a quaternary and three tertiary stereogenic centers in a one-pot multistep reaction sequence. Investigation of a collection of the secoyohimbanes in primary rat hippocampal neurons and embryonal stem cell-derived motor neurons led to discovery of compounds that promote neurite outgrowth and influence the complexity of neuronal network formation.
