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Total Synthesis of Diverse Tetramic Acid Bearing cis-Decalin Natural Products |
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| Authors: | Haoran Dong Dachao Hu Dr. Benke Hong Dr. Jin Wang Prof. Dr. Xiaoguang Lei |
| Affiliation: | 1. Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking University, Beijing, 100871 P. R. China These authors contributed equally to this work.;2. Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing, 100871 P. R. China These authors contributed equally to this work.;3. Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking University, Beijing, 100871 P. R. China |
| Abstract: | We report herein the first total syntheses of four natural antibiotics, vermisporin, PF1052/AB4015-A, AB4015-L, AB4015-B, and one hydrogenated natural product derivative, AB4015-A2, that all feature a tetramic acid bearing cis-decalin ring. The construction of the functionalized cis-decalin ring was achieved by a diastereoselective intramolecular Diels-Alder (IMDA) reaction, which proceeded via a rare endo-boat transition state. Through an intramolecular neighboring-group-oriented strategy, the sterically hindered epoxy group in vermisporin, PF1052/AB4015-A and AB4015-L was installed efficiently. A one-pot aminolysis/Dieckmann condensation cascade using l -amino acid derivatives afforded the desired tetramic acid structure. The total synthesis led to the unambiguous verification of the absolute configuration of these natural products. |
| Keywords: | Cis-Decalin Epoxidation Intramolecular Diels-Alder Reaction Natural Products Total Synthesis |