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

Angew Chem Int Ed Engl. 2022 Sep 26;61(39):e202206746. doi: 10.1002/anie.202206746. Epub 2022 Aug 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Pyridines / chemistry
  • Seaweed* / microbiology
  • Symbiosis
  • Ulva* / genetics
  • Ulva* / metabolism
  • Ulva* / microbiology


  • Pyridines
  • thallusin