title: Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues.
abstract: Neurotrophic natural products hold potential as privileged structures for the development of therapeutic agents against neurodegeneration. However, only a few studies have been conducted to investigate a common pharmacophoric motif and structure-activity relationships (SARs). Here, an investigation of structurally more simple analogues of neurotrophic sesquiterpenes of the illicium family is presented. A concise synthetic route enables preparation of the carbon framework of (±)-Merrilactone A and (±)-Anislactone A/B on a gram scale. This has allowed access to a series of structural analogues by modification of the core structure, including variation of oxidation levels and alteration of functional groups. In total, 15 derivatives of the natural products have been synthesized and tested for their neurite outgrowth activities. Our studies indicate that the promising biological activity can be retained by structurally simpler natural product analogues, which are accessible by a straightforward synthetic route.
authors.affiliation: Department Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85747, Garching, Germany.
authors.forename: Johannes
authors.identifier: http://orcid.org/0000-0002-4914-4342
authors.initials: J
authors.lastname: Richers
authors.affiliation: Catalysis Research Center, Technical University of Munich, Ernst-Otto-Fischer-Strasse 1, 85747, Garching, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pöthig
authors.affiliation: Catalysis Research Center, Technical University of Munich, Ernst-Otto-Fischer-Strasse 1, 85747, Garching, Germany.
authors.forename: Eberhardt
authors.initials: E
authors.lastname: Herdtweck
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sippel
authors.affiliation: Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hausch
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland.|Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058, Basel, Switzerland.
authors.forename: Konrad
authors.identifier: http://orcid.org/0000-0002-3351-6121
authors.initials: K
authors.lastname: Tiefenbacher
mesh_terms: D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D029523:Illicium / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D012717:Sesquiterpenes
keywords: biological activity; natural products; neurotrophic; sesquiterpenes; synthesis