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Darwinolide_ChemRxiv.pdf (7.33 MB)
Synthesis of (+)-Darwinolide, a Biofilm-Penetrating Anti-MRSA Agent
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submitted on 16.11.2018 and posted on 16.11.2018by Thomas Siemon, Simon Steinhauer, Mathias 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.