Final synthetic hurdle cleared for sarain A

Reniera sarai, a Mediterranean sea sponge, is a rich source of structurally complex alkaloids called sarains that have antibacterial, insecticidal, and antitumor activities. The compounds feature a diazatricyclic core and two macrocyclic side rings that several competing research groups have tried to synthesize for more than a decade. For sarain A (shown), intermediates containing the core structure and the saturated macrocyclic ring have been made, but attempts to further construct the more intricate macrocyclic ring containing the diol and triene functionalities have been thwarted. Neil K. Garg, Sheldon Hiebert, and Larry E. Overman of the University of California, Irvine, now report the key final steps needed to generate the second ring (Angew. Chem. Int. Ed., published online March 27, dx.doi.org/10.1002/anie.200600417). The team used a palladium-catalyzed Stille coupling between tin and iodine to close the triene ring and a subsequent oxidation-deprotection sequence to generate the aldehyde and diol functional groups.