UC Santa Barbara

Natural products have always been a classic source of new treatments against diseases. Recently, the Darwinellidae family of Antarctic sea sponges have yielded a family of molecules with high potency against diseases with poor or no current treatment.1 Darwinolide has been shown to penetrate MRSA bacterial biofilms, while the six-membered ring variants have been shown to be active against Leishmaniasis and Malaria.1 These compounds can revolutionize treatments, but are difficult to make individually. A single, robust pathway toward the entire family will allow for the synthesis of related structures that can be tested for similar disease efficacy. The synthetic efforts described in this thesis will enable rapid construction of the common core structure and subsequent access to all family members as well as bioactive analogues.