MANGANESE (III) BASED OXIDATIVE FREE RADICAL CYCLIZATION

描述：氧化自由基环化反应，其中初始 氧化产生自由基，和/或氧化环状自由基 终止反应，具有相当大的合成潜力， 更高度官能化的产物可以由更简单的 前体比标准的氢化锡还原自由基 骑自行车。这项研究的目的是开发无氧化- 自由基环化成一个可靠的和通用的方法， 高度官能化的环状和多环化合物的合成。的 PI在过去十年的研究表明，这将是一个 由1，3-二羰基形成自由基的有价值的合成方法 化合物和相关的酸性底物。私家侦探最近发现 可以从单羰基化合物得到高产率的环状产物， 在某些情况下，化合物在零下80摄氏度。初步结果 这表明从酮中获得高产率，其中烯醇化 仅酮的一侧是可能的或有利的， 产品不能烯醇化，从而防止进一步氧化的 产品共轭烯酮和醛的氧化环化反应 含有不饱和侧链的化合物也以良好的产率进行。的 PI希望充分探索和发展这些反应的范围。 由于这些起始材料非常简单， 单羰基化合物的环化应该具有更宽的范围， 在合成中的实用性优于1，3-二羰基化合物。重点 的氧化自由基环化项目的发展， 新的合成方法，将广泛适用于 合成多种生物活性化合物。PI计划 使用氧化自由基环化进行短合成 gymnomitrol和upial。在这两种情况下，合成被设计成 通过简单的方法证明了这种反应的潜在效用。 合成一种适度复杂的天然产物。裸硝酚 合成只需要三个步骤，从以前制备的 中间体Upial合成利用氧化环化， 将容易获得的环己烷-1，3-二酮转化为络合的双环 二酮抗生素二萜类cyathin B3、allocyathin B2和 制备神经生长因子产生刺激剂Erinacine A 通过使用刘易斯酸催化的烯的有效的立体定向合成， 反应生成含有完整碳原子的三环二烯醇 骨架、适当的立体化学和合适的官能度， 完成合成。结构新颖的强效肝毒素 圆柱精子蛋白酶将通过将氨加入到 二烯酮，所得二胺与硫脲缩合 衍生物和环氧化物开环以构建双环胍鎓 核心的cylindrospermopsin与控制所有，但其中一个6立体声 中心.

DESCRIPTION: Oxidative free-radical cyclizations, in which the initial radical is generated oxidatively, and/or the cyclic radical is oxidized to terminate the reaction, have considerable synthetic potential since more highly functionalized products can be prepared from simpler precursors than with the standard tin hydride reductive radical cyclizations. The goal of this research is to develop oxidative free- radical cyclization into a reliable and versatile method for the synthesis of highly functionalized cyclic and polycyclic compounds. The PI's studies over the past ten years have shown that this will be a valuable synthetic method for formation of radicals from 1,3-dicarbonyl compounds and related acidic substrates. The PI has recently discovered that high yields of cyclic products can be obtained from monocarbonyl compounds at minus 80 oC under some circumstances. Preliminary results suggest that high yields are obtained from ketones in which enolization is possible or favored to only one side of the ketone and when the product can't enolize thereby preventing further oxidation of the product. Oxidative cyclizations of a conjugated enone and an aldehyde containing an unsaturated side chain also proceed in good yield. The PI wishes to fully explore and develop the scope of these reactions. Since these starting materials are very simple, the oxidative cyclization of monocarbonyl compounds should have even broader scope and utility in synthesis than those of 1,3-dicarbonyl compounds. The focus of the oxidative free radical cyclization project is the development of new synthetic methodology that will be broadly applicable in the synthesis of wide variety of biologically active compounds. The PI plans to use oxidative free-radical cyclizations for short syntheses of gymnomitrol and upial. In both cases the syntheses are designed to demonstrate the potential utility of this reaction by the simple synthesis of a moderately complex natural product. The gymnomitrol synthesis requires only three steps from a previously prepared intermediate. The upial synthesis utilizes oxidative cyclization to convert a readily available cyclohexane-1,3-dione to a complex bicyclic dione. The antibiotic diterpenes cyathin B3, allocyathin B2 and the nerve growth factor production stimulant erinacine A will be prepared by efficient, stereospecific syntheses using a Lewis acid catalyzed ene reaction to give a tricyclic dienol containing the complete carbon skeleton, proper stereochemistry and suitable functionality for completion of the syntheses. The structurally novel, potent hepatotoxin cylindrospermopsin will be synthesized by the addition of ammonia to a dienone, condensation of the resulting diamine with a thiourea derivative, and epoxide opening to construct the ticyclic guanidinium core of cylindrospermopsin with control of all but one of the 6 stereo centers.