NATURAL PRODUCT SYNTHESIS--SEQUENTIAL RADICAL REACTIONS

天然产物合成--顺序自由基反应

基本信息

批准号：
2177000
负责人：
DENNIS P CURRAN
金额：
$ 19.03万
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：
1984
资助国家：
美国
起止时间：
1984-04-01 至 1996-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2177000
关键词：
antibiotics antiviral agents camptothecin chemical group cyclization drug design /synthesis /production isoquinolines stereochemistry steroids

antibiotics antiviral agents camptothecin chemical group cyclization drug design /synthesis /production isoquinolines stereochemistry steroids

项目摘要

This proposal is divided into three subsections that are unified by the theme of using new sequences of radical reactions as key steps in the synthesis of important natural products. 1) Camptothecin: The camptothecins are among the most promising chemotherapeutic agents under development for treatment of cancer, and recently there are indications that they may represent new directions in antiretroviral (AIDS) chemotherapy. Development of an efficient total synthesis of (S)-camptothecin and its relatives is proposed. The key step is a new 4 + 1 radical annulation for the synthesis of pyrroloisoquinolines. Long range goals include the preparation of gram-quantities of important existing camptothecins and the synthesis of new analogs for testing. 2) Crinipellin: The crinipellins are a small family of tetraquinanes with antibiotic activity. The immediate goal of this project is to develop a synthesis of optically active crinipellin A by using a new type of tandem cyclization as the central reaction. Long range goals include the study of diastereoselective radical additions to dienes. 3) Steroids: The goal of this project is to develop a strategically new approach to the steroid ring system. Experiments are planned to test the idea that a macrocyclization can be followed by three successive transannular cyclizations, resulting in a one step synthesis of the steroid nucleus from acyclic precursors. A key feature of this strategy is the question of whether the conformation of the macrocyclic radicals can control the stereochemistry of the ring fusions in the transannular cyclizations.

该提案分为三个款，这些小节由将基本反应的新序列用作关键步骤的主题重要天然产品的合成。 1）Camptothecin：凸甲虫是最有希望的化学治疗剂之一癌症治疗的发展，最近有迹象它们可能代表抗逆转录病毒（AIDS）的新方向化学疗法。开发有效的总合成提出了（S） - camptothecin及其亲戚。关键步骤是一个新的4 + 1吡咯烷醇合成的根本环状。长的范围目标包括准备重要的革兰氏阴性现有的camptothecins和用于测试的新类似物的合成。 2） crinipellin：crinipellins是一个小家族，抗生素活性。该项目的直接目标是开发通过使用新型的串联串联环化为中心反应。远程目标包括研究对二enes的非映选择性根治性添加。 3）类固醇：目标这个项目的是为类固醇开发一种战略性的新方法环系统。计划进行实验来测试一个想法大环化可以跟随三连续的跨性别循环，导致类固醇核的一步合成来自无环的前体。该策略的关键特征是问题关于大环的构象是否可以控制透射循环中环融合的立体化学。