Synthetic Studies towards the Cadiolides

A novel laboratory synthesis of cadiolides was studied. Cadiolides are secondary metabolites from marine ascidians and tunicates, and they were found to have potent activity against Gram positive bacteria like Methycillin Resistant Staphylococcus Aureus (MRSA). Previous laboratory synthesis of Cadiolide B has been accomplished by 6 steps and with a 42% overall yield. However, this approach was unable to provide Cadiolide C. In this research, a synthetic approach towards Cadiolide B was planned with cheaper and more readily-available reagents, which could in principle also be adapted to construct Cadiolides A, C, D, and E. The new approach involves a key intra-molecular 5-exo-trig-cyclization step on a betaketo-ester of a dibenzylmethanol derivative. This research focused on to synthesis of the beta-keto-ester, but unexpected challenges were encountered along the way. The original approach involving acylated Meldrum’s acid will be modified to a Claisen condensation. The synthesis of the dibenzylmethanol intermediate also needs to be optimized, and a Claisen condensation approach to this intermediate is also currently in progress.