Total synthesis of apoptolidin A.

A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6'-deoxy-l-glucose, a cross-metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the polypropionate segments and sugar units were established through diastereoselective chlorotitanium enolate aldol reactions.