Stereoselective Total Synthesis of (-)-Thallusin for Bioactivity Profiling

Chemical mediators are key compounds for controlling symbiotic interactions in the environment. Here, we disclose a fully stereoselective total synthesis of the algae differentiation factor (-)-thallusin that utilizes sophisticated 6-endo-cyclization chemistry and effective late-stage sp(2)-sp(2)-couplings using non-toxic reagents. An EC50 of 4.8 pM was determined by quantitative phenotype profiling in the green seaweed Ulva mutabilis (Chlorophyte), underscoring this potent mediator's enormous, pan-species bioactivity produced by symbiotic bacteria. SAR investigations indicate that (-)-thallusin triggers at least two different pathways in Ulva that may be separated by chemical editing of the mediator compound structure.

Automated summary

Chemical mediators play a crucial role in controlling symbiotic interactions in the environment. This study presents a fully stereoselective total synthesis of (-)-thallusin, a differentiation factor in algae, and shows its potent bioactivity in Ulva mutabilis. SAR investigations suggest that (-)-thallusin triggers different pathways in Ulva that can be separated by chemical editing of the compound structure.