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Phenolic oxidation towards synthesis of bioactive cyclic peptides

酚氧化合成生物活性环肽

基本信息

批准号：
15510181
负责人：
NISHIYAMA Shigeru
金额：
$ 2.43万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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

在本研究项目中，通过采用阳极和铊（III）氧化反应作为关键步骤的酚氧化，对包括天然产物在内的生物活性物质进行了合成研究，具体如下。（1）广草酰胺的合成。A、B和D通过在二芳基醚部分的环化成功地完成。该结果与具有抗MRSA抑制活性的单环肽的发现相关联。（2）电化学产生的溴离子溴化大根香叶烯D，得到新的双环产物，并通过光谱测定了其结构。（3）苯酚衍生物的阳极氧化和随后的刘易斯酸排列的串联反应，提供了向日葵的过敏原物质向日葵酚E及其同系物沿着。研究表明，该反应的选择性是由芳香取代基的立体化学和电性决定的。在合成中间体及相关产物中，发现了比天然向日葵酚更有效的生物活性。（4）螺异恶唑啉衍生物的电化学构筑为合成螺异恶唑啉类海洋天然产物aerhoplysinin-1和calafianin提供了可能。在前期的研究中，建立了异恶唑啉向氰醇开环的新反应，并对已有的结构进行了修正。（5）通过阳极氧化带有混合卤素取代基的苯酚衍生物，成功地合成了植物来源的神经生长因子激活剂马鞭草查尔酮，其提供了甲氧基二芳基醚部分。