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

• 批准号: 6605323
• 负责人: CRAIG S WILCOX
• 金额: $ 23.35万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/6605323
• 关键词: analytical method; chemical synthesis; chromatography; combinatorial chemistry; physical separation; solubility; technology /technique development

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）：化学分离方法应该是有效的，可扩展的，可预测的，并且易于自动化的，以增加可用候选药物的多样性，减少化学生产中产生的废弃溶剂的数量，减少人类接触化学试剂，并减少化学发现的时间和成本。相标记是控制被标记分子的溶解度或色谱行为的分子片段或聚集体。相标记在候选药物组合文库的合成中是常用的。匹兹堡大学这个项目的更大目标是开发新型的相标记和从复杂混合物中分离标记分子的新方法。这个项目将研究两种新的阶段标签。第一类——蛋白质相标签——包括可以在激活时改变形状，在“有机可溶状态”和“有机不可溶状态”之间切换的分子。当含有标记和未标记分子的混合物被激活时，只有标记的分子沉淀。我们称这样的标签为“沉淀”——这是变形相标签的第一个例子。本项目将研究两种类型的蛋白质相标签：(1)基于二苯乙烯的可回收沉淀物，用于控制有机溶解度；(2)用于控制水溶性的新型蛋白质相标签。第二种新的相标签——分选标签*——是基于简单低聚物的，这里标为(X)N。我们的目标是证明N标记分子的混合物，RN-O-(X)N,（其中rn代表分子，(X)N代表N相标签）可以在一个容器中同时进行反应，并且在反应完成后，N分子可以作为混合物被分离出来用于后续反应，或者很容易分离以提供N纯产物。分类标签和目标技术将补充和扩展含氟混合物合成，这是Curran在该部门开创的一种方法。这些方法将通过分子文库合成和沉淀结合试剂的开发、用于液相合成的新清除剂进行测试，并可以扩展到创建用于催化剂回收或金属清除的新配体。*【排序:1。按班安排。2. 分离：与他人分离[