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Synthesis of (+)‐Darwinolide, a Biofilm‐Penetrating Anti‐MRSA Agent
Author(s) -
Siemon Thomas,
Steinhauer Simon,
Christmann Mathias
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201813142
Subject(s) - desymmetrization , aldol reaction , biofilm , natural product , sponge , chemistry , stereochemistry , staphylococcus aureus , antibiotics , combinatorial chemistry , microbiology and biotechnology , enantioselective synthesis , biology , bacteria , biochemistry , catalysis , botany , genetics
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.