Practical Stereoselective Synthesis of Eribulin Fragment toward Building a Hybrid Macrocyclic Toolbox

A practical stereoselective synthesis to obtain the substituted furan ring as the substructure of eribulin is developed. An asymmetric <i>syn</i>-aldol and intramolecular oxy-Michael were two key steps in our approach. The functionalized furan derivatives were then utilized further to build the 14- and 12-membered macrocyclic diversity as <i>trans</i>- and <i>cis</i>-fused (C-29 and C-30) compounds. This is the first report of building a chemical toolbox with macrocyclic small molecules having <i>trans</i>- or <i>cis</i>-fused 14- or 12-membered rings containing the substructure of eribulin and its diastereomer