Total Synthesis of(-)-Laulimalide:Pd-Catalyzed Stereospecific Ring Construction of the Substituted 3,6-Dihydro[2H]pyran Units

摘要

Laulimalide(1;Scheme 1)is a novel cancer-therapy agent isolated from the marine sponges Hyattella sp.and Caco-spongia mycofijiensis Initially,1 received considerable attention for its potent microtubulin-stabilizing profile,similar to that of taxol with a potency against multidrug-resistant cells at nanomolar concentrations.Recently 1 received additional attention because it seems to have a binding site distinct from that of taxol at the tubulin polymers,which opens up the possibility of using it together with taxol as an enhanced treatment.