McCabe Stephanie R, Wipf Peter
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Org Biomol Chem. 2016 Jul 7;14(25):5894-913. doi: 10.1039/c6ob00878j. Epub 2016 May 24.
This review highlights noteworthy synthetic and biological aspects of the clavine subfamily of ergot alkaloids. Recent biosynthetic insights have laid the groundwork for a better understanding of the diverse biological pathways leading to these indole derivatives. Ergot alkaloids were among the first fungal-derived natural products identified, inspiring pharmaceutical applications in CNS disorders, migraine, infective diseases, and cancer. Pergolide, for example, is a semi-synthetic clavine alkaloid that has been used to treat Parkinson's disease. Synthetic activities have been particularly valuable to facilitate access to rare members of the Clavine family and empower medicinal chemistry research. Improved molecular target identification tools and a better understanding of signaling pathways can now be deployed to further extend the biological and medical utility of Clavine alkaloids.
本综述重点介绍了麦角生物碱棒麦角碱亚家族在合成及生物学方面的显著特点。近期关于生物合成的见解为更好地理解导致这些吲哚衍生物的多样生物途径奠定了基础。麦角生物碱是最早被鉴定出的真菌衍生天然产物之一，激发了其在中枢神经系统疾病、偏头痛、感染性疾病和癌症方面的药物应用。例如，培高利特是一种半合成棒麦角碱生物碱，已被用于治疗帕金森病。合成活动对于获取棒麦角碱家族的稀有成员以及推动药物化学研究尤为重要。现在可以利用改进的分子靶点识别工具以及对信号通路的更好理解，进一步拓展棒麦角碱生物碱的生物学和医学应用。
