title: Highly enantioselective catalytic synthesis of neurite growth-promoting secoyohimbanes.
abstract: 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.
authors.affiliation: Abteilung Chemische Biologie, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Andrey P
authors.initials: AP
authors.lastname: Antonchick
authors.forename: Sara
authors.initials: S
authors.lastname: López-Tosco
authors.forename: Juan
authors.initials: J
authors.lastname: Parga
authors.forename: Sonja
authors.initials: S
authors.lastname: Sievers
authors.forename: Markus
authors.initials: M
authors.lastname: Schürmann
authors.forename: Hans
authors.initials: H
authors.lastname: Preut
authors.forename: Susanne
authors.initials: S
authors.lastname: Höing
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.forename: Jared
authors.initials: J
authors.lastname: Sterneckert
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D055162:Biocatalysis; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism*; D000078183:Oxindoles; D051381:Rats; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D032070:Uncaria / Q000737:chemistry
chemical_list: D000470:Alkaloids; D026121:Indole Alkaloids; D000078183:Oxindoles; D013141:Spiro Compounds; C052714:rhyncophylline