Total Synthesis of Aporphine Alkaloids via Photocatalytic Oxidative Phenol Coupling and Biological Evaluation at the Serotonin 5-HT and Adrenergic α Receptors.

Aporphine alkaloids are important natural products with uses ranging from traditional Chinese herbal medicine to modern clinical applications. These compounds are isolated from a variety of plants and possess many powerful biological properties. Inspired by the biomimetic coupling of reticuline, we designed a novel synthetic approach to construct the corytuberine (8-2' coupling) and isoboldine (8-6' coupling) aporphine cores using a key photochemical intermolecular oxidative phenol coupling. With a short and efficient synthetic sequence telescoping of several intermediates (no chromatography) and minimal use of transition metals, we were able to functionalize these natural products into a variety of synthetic analogues. This fueled biological evaluation of the natural products and their derivatives for binding affinity at the serotonin 5-HT and adrenergic α receptors.