New Concepts, Methodologies and Scaffolds for Diversity-Oriented Organic Synthes

面向多样性的有机合成的新概念、方法论和支架

• 批准号: 7925688
• 负责人: Peter Wipf
• 金额: $ 139.3万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925688
• 关键词: 3-Dimensional; Address; Applications Grants; Area; Arts; Automation; Biological; Biological Factors; Chemicals; Chemistry; Chromatography; Creativeness; Development; Device or Instrument Development; Ensure; Equipment; Feedback; Fishes; Genetic Programming; Goals; Individual; Industry; Libraries; Library Automation; Liquid substance; Methodology; Methods; Organic Synthesis; Peptides; Phase; Production; Protocols documentation; Quality Control; Research; S Phase; Sampling; Screening procedure; Staging; Technology; Validation; base; design; design and construction; falls; fly; innovation; insight; mimetics; nanoscale; next generation; novel; programs; scaffold; scale up; small molecule libraries; tool; virtual

DESCRIPTION (provided by applicant): The overall goal of this Center of Excellence in Chemical Methodologies and Library Development grant application is to generate novel chemical libraries based on original research carried out in the areas of synthesis and analysis of novel peptide mimetics (Project 1), the combination of innovative methods for diversity-oriented synthesis and strategic separations (Project 2), and the development and implementation of fluoropolymer-based microreactors (Project 3). Our Program will develop new separation technologies using fluorous phase synthesis strategies, design and develop microreactors for nano-scale highly parallel organic synthesis, and discover new chiral stationary phases for liquid phase chromatography. Each Project has two stages: research and application. At the research stage, new methodologies will be developed in individual research groups. At the development stage, a centralized facility, the Diversity-Oriented Synthesis (DOS) Core with convenient access to state-of-the-art automated synthesis, separation, and analysis equipment, will validate the protocols and scale-up library synthesis to access 500-10,000 single compounds per library. This arrangement will provide truly independent validation for all new methodologies and provide the Projects with immediate "real world" feedback of utility and practicality. Rigorous quality control will ensure high purity samples that will be shared with collaborators in the biological fields. This Compound Library, envisioned to be composed of ultimately >50,000 structurally diverse samples in 10-20 mg quantities, will also be accessible to outside parties from industry and academe. While academic labs have developed many new methods for library synthesis and contributed important insights toward efficient automation for library production and analysis, they have fallen short in actually producing libraries and making them accessible to non-specialized labs. Our Center Program will address this deficiency and realize a new paradigm in research validation and library scale-up. It combines the power of academic research and creativity in Chemistry with cutting-edge tools of automation in synthesis, analysis, and separation in an integrated, interdisciplinary manner that includes microscale device development and biological screening.

描述（由申请人提供）：这个化学方法论和图书馆开发授予应用的卓越卓越中心的总体目标是基于在合成和分析新型肽模拟物（项目1）的最初研究中生成新型的化学图书馆（项目1），将具有多样性的综合合成和策略分离的创新方法组合（项目2）和开发项目（cropjition 2）和实施者（comportion 2）和实施者和实施者（comportion 2）和实施者（comportion 2）和实施者（）和实施者（我们的计划将使用荧光相合成策略开发新的分离技术，设计和开发用于纳米尺度高度平行的有机合成的微反应器，并发现用于液相色谱法的新手性固定相。每个项目都有两个阶段：研究和应用。在研究阶段，将在个别研究小组中开发新的方法论。在开发阶段，集中式设施，以多样性为导向的合成（DOS）核心，可方便地访问最先进的自动合成，分离和分析设备，将验证协议和规模上的库合成以访问500-10,000个单个化合物。这种安排将为所有新方法提供真正独立的验证，并为项目提供有关实用性和实用性的立即“现实世界”反馈。严格的质量控制将确保将与生物学领域的合作者共享的高纯度样本。这个化合物图书馆被设想，最终由10-20毫克的结构上> 50,000个结构上的样品组成，也将由行业和学术界的外部政党访问。尽管学术实验室已经开发了许多新的图书馆合成方法，并为图书馆生产和分析有效自动化提供了重要的见解，但它们实际上是在实际生产的图书馆方面缺乏，并使它们可以被非专业实验室访问。我们的中心计划将解决这一缺陷，并实现研究验证和图书馆扩展方面的新范式。它将学术研究和创造力在化学中的力量与综合，分析和分离的尖端自动化工具相结合，包括综合的，跨学科的方式，其中包括显微镜设备开发和生物学筛查。