Sun research group has recently developed an efficient total synthesis of marine alkaloid norzoanthamine. The related results have been published online in Journal of the American Chemical Society (JACS), entitled Concise Synthesis of Norzoanthamine Enabled by a Set of Photochemical Transformations.

Zoanthamine natural products comprise a class of marine alkaloids distinguished by their unique heptacyclic framework. These compounds compose formidable synthetic challenges but offer a wealth of biological activities, including anti-osteoporotic, anti-inflammatory, and anti-metastatic effects. To date, three total synthesis routes have been reported, requiring 36-47 steps (LLS). The limited natural and synthetic resources, however, have become the major challenge for drug development on these bioactive natural products.

This research devised innovative synthetic strategies as well as synthetic methodologies. Enabled by a set of photochemical reactions, Sun research group realized the efficient and concise synthesis of norzoanthamine in 16 steps, marking it the shortest synthesis (reported synthesis, 36-47 steps) with the highest overall yield (5.4% vs. 0.0069-3.5%) and the largest synthesis scale (>200 mg vs. <40 mg).  

This study is of great significance for the developments and applications of such rare marine alkaloids. It will benefit the familial synthesis of zoanthamine alkaloids, and facilitate the subsequent studies of target discovery and bioactivity screening.

Associate professor Dr. Yu Sun is the corresponding author. Yuchen Sun and Xiao Zhang contributed equally for the work. This research was supported by the National Natural Science Foundation of China (22271055, 22101051).  

Links：https://pubs.acs.org/doi/10.1021/jacs.4c14081