Stereoselective Synthesis of C1–C18 Fragment with Macrocyclic Framework of Marine Cytotoxic (-)-Callyspongiolide

A stereoselective convergent strategy for the synthesis of the C1–C18 fragment of callyspongiolide featuring a protected 14-membered macrocyclic core is reported. This approach highlights the viability of constructing complex macrolide framework through stereoselective methods such as asymmetric alkylation and the Evans aldol reaction enabling high level of stereocontrol and sets the stage for the total synthesis of callyspongiolide. The synthesis also involves the coupling of two key fragments—an acid and an alcohol, both bearing terminal olefins—via an esterification reaction, followed by a ring-closing metathesis (RCM) reaction as the key reactions to construct the macrocycle core.