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Enantioselective Organocatalytic Synthesis of a Secoyohimbane‐Inspired Compound Collection with Neuritogenic Activity
Author(s) -
Förster Tim,
LópezTosco Sara,
Ziegler Slava,
Antonchick Andrey P.,
Waldmann Herbert
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700015
Subject(s) - stereocenter , enantioselective synthesis , neurite , scaffold , chemistry , combinatorial chemistry , alkaloid , drug discovery , stereochemistry , computational biology , biology , biochemistry , catalysis , computer science , in vitro , database
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.