Synthesis and Structure-Function Relationship Studies of Polycyclic Ether Natural Products

1.合成了18个具有神经毒性的甘比色罗结构变体，并对其生物活性进行了评价。结构-活性关系(SAR)研究揭示了表现出强大的神经毒性所必需的关键结构元素。2.通过结构类似物的全合成和评价，研究了绞股蓝素A的细胞毒性所需的结构特征。合成孔径雷达研究表明，侧链的末端官能度和分子长度是绞股蓝A细胞毒性所必需的。此外，还建立了一条合成链球菌素-B的LMNOring片段的路线。3.完成了所提出的结构的全合成。然而，^1H和^&lt；13&gt；C核磁共振谱与天然样品的谱不匹配。基于详细的核磁共振分析和提出的海洋多环醚的生物合成途径，提出了新的结构C26-epmier，并通过全合成进行了验证。4.首次完成了具有抗真菌活性的冈比亚酸A和C的非开环聚醚骨架的高收敛合成。还实现了冈比亚酸A的AB环片段的立体选择性合成。

1.We have synthesized 18 structural variants of gambierol, potent neurotoxic polycyclic ether, and evaluated their biological activity. The structure-activity relationship (SAR) studies revealed the crucial structural elements necessary for exhibiting potent neurotoxicity.2.The structural features required for cytotoxicity of gymnocin-A were investigated by the total synthesis and evaluation of the structural analogues. The SAR studies indicated that the enal functionality of the side chain as well as the molecular length were necessary for cytotoxicity of gymnocin-A. A synthetic route to the LMNOring fragment of gymnocin-B was also established.3.Total synthesis of the proposed structure of brevenal was achieved. However, the ^1H and ^<13>C NMR spectra did not match those for the natural sample. The revised structure, the C26-epmier, was proposed based on the detailed NMR analysis along with the proposed biosynthetic pathway of marine polycyclic ethers and finally validated through total synthesis. The present studies also led to determination of the absolute configuration.4.A highly convergent synthesis of the nonacyclic polyether skeleton of gambieric acids A and C, potent antifungal polycyclic ethers, was accomplished for the first time. Stereoselective synthesis of the AB-ring fragment of gambieric acid A was also achieved.