Total Syntheses of Parthenolide and Its Analogues with Macrocyclic Stereocontrol

The
first total synthesis of parthenolide (1) is described.
The key feature of this synthesis is the formation of a 10-membered
carbocylic ring by a macrocyclic stereocontrolled Barbier reaction,
followed by a photoinduced Z/E isomerization. The
biological evaluation of a small library of parthenolide analogues
(19, 33, and 34) disclosed
a preliminary structure–activity relationship (SAR). The results
revealed that the C1, C10 double bond configuration of parthenolide
has little or no effect on the activity, and the C6 and C7 configurations
of the lactone ring have a moderate impact on the activities against
some cancer cell lines.