New Phase Tags and Sorting Tags for Organic Synthesis

用于有机合成的新相标签和分类标签

基本信息

批准号：
6900325
负责人：
CRAIG S WILCOX
金额：
$ 24.3万
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：
2003
资助国家：
美国
起止时间：
2003-05-01 至 2006-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Chemical separation methods should be efficient, scalable, predictable, and readily automated to increase the diversity of available drug candidates, reduce the amounts of waste solvent produced in chemical production, reduce human exposure to chemical agents, and reduce the time and cost of chemical discovery. Phase tags are molecular fragments, or aggregates, that control the solubility or chromatographic behavior of tagged molecules. Phase tags are frequently used in the synthesis of combinatorial libraries of drug candidates. The greater objective of this project at the University of Pittsburgh is to develop new types of phase tags and new methods for separating tagged molecules from complex mixtures. This project will investigate two new categories of phase tags. The first category - protean phase tags - includes molecules that can, on activation, change shape to switch between an "organic soluble state" and an "organic insoluble state". On activation of a mixture containing tagged and untagged molecules, only the tagged molecules precipitate. We call such tags "precipitons" - and these were the first example of protean phase tags. This project will study two types of protean phase tags: (1) recyclable precipitons based on stilbenes for controlling organic solubility, and (2) new protean phase tags for controlling water solubility. The second new category of phase tags - sorting tags* - is based on simple oligomers, here designated (X)N. Our objective is to demonstrate that a mixture of N tagged molecules, RN-O-(X)N, (where RNrepresent the molecules and (X)N represent the N phase tags) can be subjected to simultaneous reactions in one vessel and that after the reaction is complete the N molecules may be isolated as a mixture for a subsequent reaction, or easily separated to provide the N pure products. Sorting tags and the target technology will complement and extend fluorous mixture synthesis, a method pioneered by Curran in this department. The methods will be tested by molecular library syntheses and development of precipiton-bound reagents, new scavengers for solution phase synthesis, and can be extended to create new ligands for catalyst recovery or metal scavenging. *[Sort: 1. To arrange according to class. 2. To separate from others.]

描述（由申请人提供）：化学分离方法应具有高效，可扩展，可预测且容易自动化，以增加可用药物的多样性，减少化学生产中产生的废物溶剂量，减少人类对化学药品的暴露，并减少化学发现的时间和成本。相位标签是控制标记分子的溶解度或色谱行为的分子片段或聚集体。相标签经常用于候选药物组合文库的合成。该项目在匹兹堡大学的更大目标是开发新型的相位标签和新方法，以将标记的分子与复杂混合物分开。该项目将研究两个新类别的相位标签。第一类 - 蛋白相标签 - 包括可以在激活时改变形状以在“有机可溶性状态”和“有机不溶性状态”之间切换的分子。激活包含标记和未标记分子的混合物，只有标记的分子沉淀。我们称此类标签为“悬崖” - 这是蛋白相标签的第一个例子。该项目将研究两种类型的蛋白相标签：（1）基于高跟苯甲部控制有机溶解度的可回收悬崖，以及（2）用于控制水溶性的新蛋白相标签。相位标签的第二个新类别 - 排序标签* - 基于简单的低聚物，此处指定为（x）n。我们的目的是证明，n标记的分子的混合物rn-o-（x）n（在rn-epresent分子和（x）n代表n相标记的情况下）可以同时在一个容器中进行反应，并且在反应后可以将N分子隔离为纯净的反应，或者可以将N分子隔离为纯正的反应，或者可以将N分子隔离为纯净的反应。分类标签和目标技术将补充和扩展荧光混合物的合成，这是Curran在该部门开创的方法。该方法将通过分子库合成和悬崖结合试剂的开发，用于溶液相合成的新清除剂的开发，并可以扩展以创建用于催化剂恢复或金属清除的新配体。 *[排序：1。按课程安排。 2。与他人分开。]