Applications of Electron Transfer Initiated Cyclizations

本提案的目的是继续发展电子转移引发的环化反应，并将这种方法用于合成生物学上重要的结构。在这个反应中，光引发的单电子氧化在均酶位置上被一个供电子取代基取代的烷基芳烃产生含有明显减弱和极化的苯基碳-碳键的自由基阳离子。附加的亲核试剂，如羟基、醚和酰胺基团可以取代苯基，导致环化反应。单电子转移反应温和的反应条件和独特的化学选择性使该反应成为构建有机分子的一种潜在的非常强大的新方法。该项目的具体目标包括：对该反应耐受的阳离子稳定取代基、芳香离去基和亲核试剂的类型进行深入研究。这项研究包括开发新的杂生级联反应。化学反应：化学上引起的反应变体的发展电子转移引发的聚合物载体环释放反应的发展。利用该反应作为关键步骤，从pederin和mycalamide家族中合成有效的抗肿瘤和免疫抑制剂，并在合成类似物中使用这些序列。该方案既提供了有机合成的新方法，又提供了具有挑战性和重要医学结构的有效途径。

The purpose of this proposal is to continue the development of the electron transfer initiated cyclization reaction and to use this methodology for the synthesis of biologically important structures. In this reaction the photoinitiated single electron oxidation of alkylarenes substituted at the homobenzylic position with an electron donating substituent produces radical cations containing substantially weakened and polarized benzylic carbon-carbon bonds. Appended nucleophiles, such as hydroxyl, ether, and amide groups can displace benzylic radicals, resulting in a cyclization reaction. The mild reaction conditions and unique chemoselectivity exhibited by single electron transfer make this reaction a potentially very powerful new method for constructing organic molecules. Specific goals for the project include: A thorough study of the types of cation stabilizing substituents, aromatic leaving groups, and nucleophiles tolerated by this reaction. This study includes the development of new heterogenerative cascade reactions. The development of a chemically initiated variant of the reaction. The development of an electron transfer initiated cyclorelease reaction from a polymer support. Employment of the reaction as the key step in brief total syntheses of potent antitumor and immunosuppressant agents from the pederin and mycalamide family, and the use of these sequences in the synthesis of analogs. The proposed program provides both new methodology for organic synthesis and efficient routes to challenging and medicinally important structures.