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

Abstract

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 sp² -sp² -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.

Keywords: Algae; Biological Activity; Structure-Activity Relationships; Terpenoids; Total Synthesis.