A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin B

A unified synthetic route for the total syntheses of eribulin and a macrolactam analog of halichondrin B is described. The key to the success of the current synthetic approach includes the employment of our reverse approach for the construction of cyclic ether structural motifs and a modified intramolecular cyclization reaction between alkyl iodide and aldehyde functionalities to establish the all-carbon macrocyclic framework of eribulin. These syntheses, together with our previous work on the total syntheses of halichondrin B and norhalichondrin B, demonstrate and validate the powerful reverse approach in the construction of cyclic ether structural motifs. On the other hand, the unified synthetic strategy for the synthesis of the related macrolactam analog provides inspiration and opportunities in the halichondrin field and related polycyclic ether areas.

Automated summary

A unified synthetic route for the total syntheses of eribulin and a macrolactam analog of halichondrin B has been successfully developed. The synthetic strategy involves the use of a reverse approach to construct cyclic ether structural motifs and a modified intramolecular cyclization reaction to establish the carbon macrocyclic framework of eribulin. These syntheses validate the effectiveness of the reverse approach in constructing cyclic ether structural motifs and provide inspiration and opportunities in the field of halichondrin and related polycyclic ether compounds.