Spirastrellolide A is a complex marine natural product that has been shown to be a highly potent inhibitor of protein phosphatase 2A. Much like the well-known Ser/Thr phosphatase inhibitors fostriecin and okadaic acid, spirastrellolide causes premature entry into mitosis and mitotic arrest and is thus, a potential theraputic against various forms of cancer. There are however, many questions regarding the actual structure of spirastrellolide (absolute and relative stereochemistries, pharmacaphore etc.) which to date have not been answered through isolation/degredation and could likely be answered by total synthesis. The structural complexity of spirastrellolide is high, so the total synthesis would require a tremendous effort; we are proposing the stereoselective synthesis of the two spiroketal domains, and go on to suggest a general strategy with which the two pieces can be united, and the total synthesis completed. ? ? ?
