Biomimetic Total Synthesis of (±)-Gracilioether F

二零零九年， gracilioether A首次從Agelas gracilis中分離得到。自此以後，gracilioethers E 到 K相繼從海綿Plakinastrella mamillaris中被分離出來。從結構上看，這些化合物都具有共同的並三環和cyclopenta[b]furan-2-one結構。我們推斷，gracilioether家族所具有的立體化學上的同源性可能暗示它們有相同的仿生合成途徑。Gracilioether家族的獨特核心結構和它們潛在的生物活性吸引了我們的注意，所以我們開展了該家族天然產物gracilioether F的全合成研究。從簡單易得的聯烯酯出發，通過內型的狄爾思-阿爾德反應，我們得到了關鍵的1,2-二氧六環結構。我們設想，這個1,2-二氧六環結構可以作為共同的中間體，從而去合成不同的gracilioether家族天然產物。在經過X射線單晶衍射分析確定關鍵中間體的立體化學之後，通過對前面得到的1,2-二氧六環中間體進行還原裂解和隨後的氧化兩步反應得到了天然產物gracilioether F。Since the first isolation of gracilioether A from Agelas gracilis in 2009, gracilioethers E to K have been isolated from the marine sponge Plakinastrella mamillaris. Structurally, these compounds feature a common cyclopenta[b]furan-2-one moiety as well as a fused tricyclic core. We reasoned that the stereochemical homology observed from the gracilioether family may suggest a common biomimetic pathway. As such, the unique core structures of the gracilioether family, together with their potential biological activities, have drawn our attention. Therefore, we undertook synthetic studies towards the total synthesis of one of the gracilioether members, namely, gracilioether F.Starting from a readily available allenic ester, the key 1,2-dioxane structure was obtained through an endo-Diels-Alder cycloaddition between diene and singlet oxygen. It was envisaged that this 1,2-dioxane framework could serve as a common intermediate to access the total synthesis of diversified gracilioethers. After the stereochemistry of the key intermediate was confirmed by an X-ray crystallographic analysis, the biomimetic total synthesis of gracilioether F was achieved with 2 more steps via a pivotal reductive cleavage of the aforementioned 1,2-dioxane species, and a subsequent oxidation of the resulting diol.Shen, Xinyue.Thesis Ph.D. Chinese University of Hong Kong 2016.Includes bibliographical references (leaves ).Abstracts also in Chinese.Title from PDF title page (viewed on …).Detailed summary in vernacular field only.Detailed summary in vernacular field only