Applications of Electron Transfer Initiated Cyclizations

电子转移引发环化的应用

基本信息

批准号：
6609734
负责人：
Paul E Floreancig
金额：
$ 23.73万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2007-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6609734
关键词：
antineoplastics antiviral agents biological products chemical group chemical synthesis cyclization cycloalkene electron transport polymers

项目摘要

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.

该提案的目的是继续开发电子转移引发的环化反应，并使用该方法来合成生物学上重要的结构。在该反应中，在均苯甲基位置被给电子取代基取代的烷基芳烃的光引发单电子氧化产生含有显着弱化和极化的苯甲基碳-碳键的自由基阳离子。附加的亲核基团，例如羟基、醚基和酰胺基团可以取代苄基，导致环化反应。单电子转移所表现出的温和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潜在非常强大的新方法。该项目的具体目标包括：彻底研究该反应所耐受的阳离子稳定取代基、芳香族离去基团和亲核试剂的类型。这项研究包括新的多相级联反应的开发。开发化学引发的反应变体。电子转移的发展引发了聚合物载体的环释放反应。使用该反应作为来自佩德林和麦卡拉酰胺家族的有效抗肿瘤和免疫抑制剂的简单全合成的关键步骤，以及这些序列在类似物合成中的用途。拟议的计划既提供了有机合成的新方法，也提供了具有挑战性和医学上重要结构的有效途径。