Total Synthesis of (+)-Complanadine A Using an Iridium-Catalyzed Pyridine C−H Functionalization

摘要

The Lycopodium alkaloids are among the most skeletally diversenfamilies of natural products that have been isolated to date.n1nInnaddition to their complex architecture, many of the alkaloids innthis family possess potentially useful biological activity, whichnincludes acetylcholinesterase (AChE) inhibition.n2nThe utility ofnknown AChE inhibitors, such as the Lycopodium alkaloid huperzinenA(1, Figure 1),n3nto partially address the treatment of Alzheimer’sndisease is supported by the observation of increased memory andnlearning in rats upon administration of 1.n4nFurthermore, severalnAChE inhibitors, including galanthamine5nand Aricept,n6nare com-nmercial pharmaceuticals that are used to treat Alzheimer’s diseasenindications. However, because AChE inhibition appears to treat onlynthe symptoms of neurodegenerative diseases, there continues to bena need to identify other natural products that promote the growthnof new neural networks. In this regard, Lycopodium alkaloids, suchnas the lyconadins (e.g., 3)n7nand complanadine A (4),n8nare especiallyninteresting because they enhance mRNA expression for nervengrowth factor (NGF) and the production of NGF in human glialncells.