Costunolide structure

In addition to its importance for inflammatory responses, NF-kB also plays a role in the regulation of cell homeostasis and apoptosis [62-64] and it was thus straightforward to assume a link between the known cytotoxic activity of STLs and their NF-kB inhibitory activity [3], It was demonstrated that helenalin indeed induces apoptosis and that it does so via a CD95 death receptor independent pathway and requires the activation of caspases [43], Further STLs for which quite detailed studies on pro-apoptotic activity and mechanism exist are the germacronolides parthenolide and costunolide (structures 32 and 52 in Fig. (9)) [44, 45]. 

The bioactivity of costunolide (19) in both the DNA-damaging yeast bioassay and the cytotoxicity assay has led to the suggestion that it acted by interaction with DMA in some manner. The lack of DNA-damaging activity of the structurally related (-)-frullanolide (21) has led to the conclusion that the focus of activity in 19 is not simply the a, -unsaturated lactone moiety as suspected in many other cytotoxicity studies with a-methylene-Y-lactones [32]. 

Structure and absolute configuration of a new hydroxycostunolide (407) from Porella species 65) were elucidated mainly by comparison of its H-NMR spectrum with that of a co-metabolite, costunolide (406), and tamaulipin B ( = 3a-hydroxycostunolide) (413) from Ambrosia species (Compositae) 347). Acetylation of (407) gave novanin (412) with a 3 3-acetoxyl group. This was followed by cyclization with SOCI2 to afford cyclonovanin A (414) (i70), as shown in Scheme 50. Thus, the new germacranolide was formulated as (407). 

---