Synthesis of (+)-Darwinolide, a Biofilm-Penetrating Anti-MRSA Agent
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 tr...
| Main Authors: | , , |
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| Format: | Other/Unknown Material |
| Language: | unknown |
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American Chemical Society (ACS)
2018
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| Online Access: | http://dx.doi.org/10.26434/chemrxiv.7352459.v1 https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73f5d567dfeca98ec39e3/original/synthesis-of-darwinolide-a-biofilm-penetrating-anti-mrsa-agent.pdf |
| Summary: | 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. |
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