Phenolic oxidation towards synthesis of bioactive cyclic peptides

本课题以阳极氧化反应和铊（III）氧化反应为关键步骤，进行酚氧化合成生物活性物质的研究，包括天然产物。(1)欧酰胺类化合物的合成。A、B和D是通过二芳基醚的环化成功完成的。这一结果与单环肽对MRSA的抑制活性有关。(2)由溴离子电化学生成的锗烯D的溴化反应，提供了新的双环产物，并对其结构进行了光谱测定。(3)苯酚衍生物的阳极氧化串联反应，再加上路易斯酸排列，产生了向日葵的致敏物质向日葵醇E及其同系物。研究表明，排列反应的选择性是由芳取代基的立体化学和电性决定的。在合成中间体和相关产物中，观察到比天然向日葵醇更有效的生物活性。(4)螺异恶唑啉衍生物的电化学构建使得合成螺异恶唑类海洋天然产物气参素-1和calafianin成为可能。在前一种研究中，建立了异恶唑啉对氰醇的新开环，并对报道的结构进行了修正。(5)植物源性神经生长因子的活化剂马尾草甲酮（Verbenachalcone），通过阳极氧化法制备了含混合卤素取代基的苯酚衍生物，得到了甲氧基二芳基醚基团

Synthetic studies on bioactive substances including natural products by phenolic oxidation employing anodic and thallium (III) oxidation reactions as key steps, was undertaken in this research project, as follows. (1)Synthesis of eurypamides. A, B, and D was successfully accomplished by the cyclization at the diaryl ether moieties. This result attached with findings of mono-cyclic peptide carrying the inhibitory activity against MRSA. (2)Bromination of germacrene D by bromonium ion electrochemically generated, provide the new bicyclic products, structures of which were spectroscopically determined. (3)The tandem reaction involving anodic oxidation of phenol derivatives, followed by the Lewis acid arrangement, provides heliannuol E, an alleropathogenic substance of sunflower, along with its congeners. This investigation revealed that the selectivity of the arrangement reaction is conducted by stereochemistry and electric character of aromatic substituents. More effective biological activity than that of natural heliannuols, was observed among synthetic intermediates and related products. (4)The electrochemical construction of the spiroisoxazoline derivatives made it possible to synthesize aerhoplysinin-1 and calafianin, spiroisoxazoline-class marine natural products. In the former investigation, the new ring-opening of the isoxazoline to the cyanohydrin was established, and the revision of the reported structure was undertaken. (5)Verbenachalcone, an activator of the nerve-growing factor of plant origin, was successfully synthesized by anodic oxidation of phenol derivatives carrying mixed halogen-substituents, which provided a methoxy diaryl ether moiety.0