Synthesis of (+)‐Darwinolide, a Biofilm‐Penetrating Anti‐MRSA Agent
Abstract Darwinolide, a recently identified marine natural product from the Antarctic sponge Dendrilla membranosa, was previously shown to exhibit promising activity against the biofilm phase of methicillin‐resistant Staphylococcus aureus. Its challenging tetracyclic rearranged spongian diterpenoid...
| Published in: | Angewandte Chemie |
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| Main Authors: | , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2018
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1002/ange.201813142 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fange.201813142 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.201813142 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.201813142 |
| Summary: | Abstract Darwinolide, a recently identified marine natural product from the Antarctic sponge Dendrilla membranosa, was previously 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 tetrahydrofuran units. Herein, we describe the first synthesis of (+)‐darwinolide, which features 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. |
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