Total synthesis of apoptolidin: construction of enantiomerically pure fragments

A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is decribed. The first and second generation synthesis to the required fragments for apoptolidin (1) is described.