Total Synthesis\nof Eribulin, a Macrocyclic Ketone\nAnalogue of Halichondrin B, via Prins Macrocyclization

An entirely chromium-free synthesis of eribulin, a fully\nsynthetic\nmacrocyclic ketone analogue of the marine natural product halichondrin\nB, was achieved through iterative sulfone fragment couplings followed\nby an intramolecular Prins reaction involving a C.26 homoallenyl alcohol\nand a C.27 aldehyde acetal. A notable feature of this new macrocyclization\nis the employment of a β-ketosulfone at C.15/14 as an acid-stable\nprogenitor of the notoriously acid-sensitive polycyclic ketal moiety,\ncharacteristic of the halichondrins.