Total Synthesis of Aporphine Alkaloids via Photocatalytic Oxidative Phenol Coupling and Biological Evaluation at the Serotonin 5‑HT2 and Adrenergic α1A 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-HT2 and adrenergic α1A receptors.