Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustr. 3, 14195, Berlin, Germany.
Angew Chem Int Ed Engl. 2019 Jan 21;58(4):1120-1122. doi: 10.1002/anie.201813142. Epub 2018 Dec 18.
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.
达乌里醇内酯是一种从南极海绵 Dendrilla membranosa 中分离出的海洋天然产物，先前的研究表明其对耐甲氧西林金黄色葡萄球菌的生物膜阶段具有良好的活性。其具有挑战性的四环重排海绵二萜结构将一个三甲基环己基单元与一个具有两个融合的四氢呋喃单元的七元核心连接起来。本文描述了 (+)-达乌里醇内酯的首次全合成，其关键步骤包括缩合片段偶联、Ireland-Claisen 重排和有机催化的非对映选择性去对称化。我们的研究结果为开发新型抗生物膜特异性抗生素奠定了基础。
