权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on the Synthesis of Dynemicin Analogues and their Reaction Mechanisms

动力霉素类似物的合成及其反应机理的研究

基本信息

批准号：
07457521
负责人：
SHIBUYA Masayuki
金额：
$ 4.99万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457521/
关键词：
enyne-allene synthesis enzyme-inhibition cascade Dynemicin radical Vitamin B6 エンジイン DNA 切断

项目摘要

Dynemicins possessing the characteristic cis-hex-3-ene-1,5-diynyl group have attracted considerable attention due to the generation of a phenylene biradical which is responsible for DNA strand scission. Designing the structurally simplified enediyne congeners retaining the impressive DNA cleaving properties is of great importance for potential use in chemotherapy or as tools for biotechnology. Ongoing research concerned with the development of bioactive enediyne mimics has required large quantities of acyclic enediynes. We initiated the research for the convenient and practical synthesis of of the open chain enediyne derivatives by simple elimination of tert-hydroxy group. By using above method, we synthesized several model enediynes which produce biradical species via enyne-allene intermediates. One of them is the model compounds which produce biradicals under acidic conditions, and the other is the enediynes which produce biradicals by ester-hydrolysis. Both model compounds produced carbon biradicals by their characteristic cascade reactions initiated by triggering devices. On the way of these investigations, we found that the biradicals transformed into zwitterionic species, and this reaction mechanisms were investigated. On the other hand, the acyclic enediyne possessing an aminomethyl group was designed and synthesized as a potential substrate for pyridoxal-dependent enzymes. This compound was shown to give cycloaromatized products by the reaction with pyridoxal or isonicotinaldehyde via the toluene biradical intermediate.

具有特征性顺式-己-3-烯-1，5-二炔基的动力霉素由于产生负责DNA链断裂的亚苯基双自由基而引起相当大的关注。设计结构简化的烯二炔同系物保留令人印象深刻的DNA切割性能是非常重要的潜在用途在化学治疗或作为生物技术的工具。正在进行的关于开发具有生物活性的烯二炔模拟物的研究需要大量的无环烯二炔。本论文首次开展了通过简单的叔羟基消去法合成开链烯二炔衍生物的研究。利用上述方法，我们合成了几种通过烯炔-联烯中间体产生双自由基的模型烯二炔。一类是在酸性条件下产生双自由基的模型化合物，另一类是通过酯水解产生双自由基的烯二炔。这两种模型化合物产生的碳双自由基的特征级联反应引发的触发装置。在这些研究的过程中，我们发现双自由基转化为两性离子物种，并对此反应机理进行了探讨。另一方面，设计并合成了具有氨甲基的无环烯二炔作为吡哆醛依赖性酶的潜在底物。该化合物通过与吡哆醛或异烟醛反应，经由甲苯双自由基中间体，显示出环芳构化产物。