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Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues
Author(s) -
Richers Johannes,
Pöthig Alexander,
Herdtweck Eberhardt,
Sippel Claudia,
Hausch Felix,
Tiefenbacher Konrad
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201605362
Subject(s) - natural product , chemistry , structural motif , neurotrophin , neurite , stereochemistry , sesquiterpene , sesquiterpene lactone , structure–activity relationship , combinatorial chemistry , biochemistry , in vitro , receptor
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.