Total Synthesis of a Marine Bromotriterpenoid Isodehydrothyrsiferol

Abstract

AbstractThe thyrsiferol family natural products are marine triterpene polyethers biogenetically derived from squalene and structurally characterized by a bromine atom and some six- and five-membered ethereal rings. Their stereostructures cannot easily be determined by modern spectroscopic analysis, because there are acyclic tetrasubstituted chiral centers and the remote stereoclusters. In these cases, asymmetric total synthesis demonstrates its power. Herein, to determine the entire stereostructure of the thyrsiferol family member isodehydrothyrsiferol, isolated from the red alga Laurencia viridis, the asymmetric total synthesis has been performed. The key steps are the convergent and effective synthetic strategy using a Suzuki–Miyaura cross-coupling, a one-pot construction of the tetrahydropyranyl C ring via a stoichiometric Katsuki-Sharpless asymmetric epoxidation and 6-exo oxacyclization in situ promoted by Ti chelation, and 6-endo bromoetherification for the A ring formation. Through the enantioselective total synthesis, we have accomplished complete assignment of the entire stereostructure for isodehydrothyrsiferol and found the absolute configuration of the ABC ring system is opposite to that common to the other congeners from the same red algae. In addition, such enantiodivergency also occurred between dehydrothyrsiferol and isodehydrothyrsiferol originating from the identical red alga Laurencia viridis. There are no these findings without asymmetric total synthesis.