模拟四氢叶酸辅酶的结构与功能生物体外转移直链四个碳单元

Transfer of Four Carbon Units in Outside the Body by Mimicking the Function of One Carbon Transfer of the Tetrahydrofolate Coenzyme

本文合成了新的四氢叶酸辅酶模型:碘化1-甲基-2-丙基-3-苯磺酰基咪唑啉(10),研究了它们的反应性能.发现模型化合物与双官能团亲核体邻苯二胺,邻氨基苯酚反应,完全转移了四个碳的正丁基单元,实现了四个碳单元的体外完全转移,模拟了四氢叶酸辅酶的结构与转移基团的功能,获得了合成2-丙基取代苯并咪唑和2-丙基取代苯并噁唑的新方法.四氢叶酸辅酶模型10与单官能团亲核体氨类作用,如苯胺、对甲基苯胺、对甲氧基苯胺、对氯苯胺,部分转移了四个碳的次丁基单元,生成了不同基团取代的N,N,N’-三取代乙二胺盐19~22,探索了这类化合物的简易合成方法.这些反应都模拟了四氢叶酸辅酶在生物体内转移一个碳单元的功能,扩展到四个碳原子单元体外的转移,产生了几种新的合成方法和试剂,可应用到有机合成中.

1-Methyl-2-propyl-3-benzenesulfonyl imidazolidinium iodide(10)was prepared as the tetrahydrofolate model compound at the oxidation level of formate,which reaction property had been researched.It was found that model 10 reacted with bifunctional nucleophiles such as o-phenylenediamine,2-aminophenol to transfer the butyl,leading to transfer of four carbon fragments completely in outside the body and mimicking function of one carbon unit transfer of the tetrahydrofolate coenzyme,and finding a synthetic way directly toward benzimidazoles,benzoxazoles.The reaction of the model 10 with monofunctional nucleophiles such as amine(aniline,p-methylaniline,p-methoxyaniline and p-chloroaniline)afforded the products 19~22,which were part transfer products of four carbon fragments,N,N,N-trisubstituted ethylenediamine salt containing three different groups.A simple synthetic method of these type compounds has been explored.The procedure have mimicked the function of biochemical transfer of one carbon fragment of the tetrahydrofolate coenzyme,and expanded it to four carbon units transfer in outside the body,leading to a few of new synthesis methods and reagents,which can be applied to organic synthesis.