Microtubule-stabilizing marine metabolite laulimalide and its derivatives:: Synthetic approaches and antitumor activity

Laulimalide has attracted significant attention in both the synthetic organic and the medicinal communities. A variety of total syntheses was accomplished within the last 3 years. Problems arising from the presence of the (Z)-enoate and the epoxide were overcome by novel macrocrystallization strategies and by stereoselective last-step epoxidation. Due to the lack of material, the in vivo evaluation of laulimalide and of the few analogues which have been synthesized to date has not yet been possible. However, as short and economical solutions for the construction of main fragments and their conjunction have been developed, it will be possible to design and synthesize further analogues that might be helpful to identify the critical structural features necessary for improved stability and biological activity.