Synthetic studies toward southern half of spirastrellolide A using ketal-tethered ring closing metathesis (RCM).

Ring-closing metathesis (RCM) represents the one of the most important strategies in synthetic organic chemistry. It has come to our attention that despite being well known entities, acetals or ketals have not been extensively utilized as tethers. The unconventional ketal-tethered RCM was investigated to achieve the spiroketal moiety in our previous study. Through cyclic ketal formation catalyzed by Tf2NH, thermodynamically stable spiroketal system was accomplished via the most favored intermediate by ketal-tethered RCM. In our pursuit of ketal-tethered RCM reaction, spirastrellolide A was an attractive synthetic target. Spirastrellilide A was isolated from caribbean marine sponge spirastrella coccinea, was discovered as a new antimitotic natural product. Spirastrellolide A through cell-based screening has shown a potent inhibitory activity against protein phosphatase 2A [IC 50 = 1 nM] and excellent selectivity for PP2A over PP1 [ratio of IC 50 = 1:50]. Therefore we became interested in our synthetic efforts toward spirastrellolide A. The intriguing spirastrellolide A is comprised of tetrahydropyran A ring and spiroketal BC ring in the southern half. We have demonstrated our synthetic efforts toward the southern half synthesis of spirastrellolide A.