Antonchick Andrey P, López-Tosco Sara, Parga Juan, Sievers Sonja, Schürmann Markus, Preut Hans, Höing Susanne, Schöler Hans R, Sterneckert Jared, Rauh Daniel, Waldmann Herbert
Abteilung Chemische Biologie, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Chem Biol. 2013 Apr 18;20(4):500-9. doi: 10.1016/j.chembiol.2013.03.011.
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.
具有神经调节活性的天然产物及其潜在的结构骨架可能会启发新型神经营养化合物类别的合成。螺环异育亨宾生物碱钩藤碱是中国传统医学中用于治疗中枢神经系统疾病的钩藤属植物提取物的主要成分。基于钩藤碱的结构，开发了一种高度对映选择性和高效的有机催化合成方法，该方法可通过一锅多步反应序列获得四环异育亨宾骨架，其中包含一个季碳和三个叔碳立体中心。对一系列异育亨宾在原代大鼠海马神经元和胚胎干细胞衍生的运动神经元中的研究，发现了能够促进神经突生长并影响神经网络形成复杂性的化合物。
