Total Synthesis of Apoptolidin: Part 1. Retrosynthetic Analysis and Construction of Building Blocks

Abstract
No less than 30 stereogenic elements, a highly unsaturated 20-membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin (1) a challenging synthetic target. The retrosynthetic analysis revealed five key building blocks—three for the construction of the macrolide ring B and two prospective pendant saccharide units—which were synthesized in a highly convergent manner and then connected. Apoptolidin's rather labile nature proved particularly challenging in the final deprotection, purification, and characterization procedures.