The first fully enantioselective catalytic synthesis of the algal morphogen (−)-thallusin employs polyene cyclization chemistry with a novel, regioselective terminator. The ee of biosynthesized thallusin was determined. Fe(III)-transport studies demonstrate independence of iron uptake and morphogenic activity, suggesting the Fe(III)-complex of thallusin being of importance primarily for compound resorption.

Abstract

A fully enantioselective, catalytic synthesis of the algal morphogen (−)-thallusin using polyene cyclization chemistry is reported. The synthesis features dedicated precursor design, introduction of a TMS-substituted arene as a regioselective terminator, very high enantiomer excess (ee) on gram scale, and productive scaffold functionalization. Furthermore, an ee determination methodology of thallusin samples was developed, and the ee of biosynthesized thallusin was determined. Fe(III)-uptake studies demonstrated that the cellular uptake of iron facilitated by thallusin derivatives was independent of their morphogenic activity, suggesting their active import via siderophore transporters as a shuttle system.