Get access

Total Synthesis of the Tubulin Inhibitor WF-1360F Based on Macrocycle Formation through Ring-Closing Alkyne Metathesis


  • This work was supported by the Swiss National Science Foundation (SNF) (Project 200021_126511). We are very grateful to Prof. Dr. Alois Fürstner, MPI für Kohlenforschung, Mülheim (Germany), for the generous donation of samples of his catalysts.


original image

Key steps in this total synthesis of the antimitotic natural product WF-1360F (3) include the formation of the macrocycle through ring-closing alkyne metathesis and the subsequent conversion of the ensuing alkyne moiety into an E-configured double bond. As illustrated by the synthesis of 4, the macrocyclic vinyl iodide 2 can also serve as a common precursor for the synthesis of side-chain-modified rhizoxin analogues (see scheme; TIPS=triisopropylsilyl).