MANGANESE (III) BASED OXIDATIVE FREE RADICAL CYCLIZATION

描述：氧化自由基环化反应，其中最初的 自由基被氧化生成，和/或环状自由基被氧化 为了终止反应，具有相当大的合成潜力，因为 更高功能化的产品可以从SIMPLE 前驱体比标准氢化锡还原自由基强 骑自行车运动。这项研究的目标是开发无氧化- 自由基环化成为一种可靠和通用的方法 高度官能化的环和多环化合物的合成。这个 派过去十年的研究表明，这将是一个 由1，3-二羰基合成自由基的有价值的合成方法 化合物和相关的酸性底物。私人侦探最近发现 从单羰基可以得到高产率的环状产物 在某些情况下，化合物的温度为-80oC。初步结果 建议从烯醇化的酮中获得高的产率 是可能的或只倾向于酮的一侧，并且当 产品不能烯醇化，从而防止进一步氧化 产品。共轭烯酮和醛的氧化环化反应 含有不饱和侧链的也以良好的产率进行。这个 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，氧化的 单羰基化合物的环化应具有更广泛的范围和 与1，3-二羰基化合物相比，在合成中的实用性更高。焦点 氧化自由基环化项目的进展是 新的综合方法学将广泛适用于 多种生物活性化合物的合成。圆周率计划 利用氧化自由基环化反应进行短程合成 健美和上流社会。在这两种情况下，合成的设计都是为了 通过简单的实验证明了该反应的潜在用途 合成一种中等复杂的天然产物。体操三项全能 合成只需要三个步骤，而以前准备的 中级的。UPU合成利用氧化环化来 将易得的环己烷-1，3-二酮转化为复杂的双环化合物 迪奥内。所述抗生素二萜类化合物Cyathin B3、Allocyathin B2和 将制备神经生长因子产生刺激剂淫羊藿碱A 通过使用Lewis酸催化的烯进行高效、立体专一性的合成 反应生成含全碳的三环二烯醇 骨骼，适当的立体化学和适当的功能 完成合成。结构新颖、强效的肝毒素 圆柱型精液蛋白的合成方法是将氨水加入到 二烯酮，生成的二胺与硫脲的缩合 衍生物和环氧化物开孔来构筑四环基团 圆柱型精液蛋白核心，控制6个立体声系统中除一个之外的所有音响 中锋。

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.