69. Synthesis of (+)-Darwinolide, a Biofilm-Penetrating Anti-MRSA Agent
T. Siemon, S. Steinhauer. M. Christmann
Darwinolide, a recently identified marine natural product from the Antarctic sponge Dendrilla membranosa, was shown to exhibit promising activity against the biofilm phase of methicillin‐resistant Staphylococcus aureus. Its challenging tetracyclic rearranged spongian diterpenoid structure links a trimethylcyclohexyl subunit to a seven‐membered core with two fused tetrahydrofurans. Here we describe the first synthesis of (+)‐darwinolide featuring a convergent aldol fragment coupling, an Ireland‐Claisen rearrangement and an organocatalytic desymmetrization as the key steps. Our results provide a foundation for the development of novel antibiofilm‐specific antibiotics.