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

描述(由申请人提供)：这项化学方法学和图书馆发展资助申请的总体目标是在以下领域开展的原创研究的基础上建立新的化学图书馆：新的多肽模拟物的合成和分析(项目1)、面向多样性的合成和战略分离的创新方法的组合(项目2)以及基于氟聚合物的微反应器的开发和实施(项目3)。我们的计划将利用氟相合成策略开发新的分离技术，设计和开发用于纳米级高度平行有机合成的微反应器，并发现新的用于液相色谱的手性固定相。每个项目都有两个阶段：研究和应用。在研究阶段，将在各个研究小组中开发新的方法。在开发阶段，一个集中的设施，即面向多样性的合成(DOS)核心，可以方便地访问最先进的自动化合成、分离和分析设备，将验证协议和扩大文库合成，以访问每个文库500-10,000个单一化合物。这一安排将为所有新方法提供真正独立的验证，并为项目提供实用性和实用性的即时“真实世界”反馈。严格的质量控制将确保高纯度的样本将与生物领域的合作者共享。这个化合物文库预计最终将由50,000个结构不同的样品组成，数量为10-20毫克，也将向来自行业和学术界的外部机构开放。虽然大学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的高效自动化提供了重要的见解，但它们在实际生产图书馆并使其可供非专业实验室访问方面做得不够。我们的中心计划将解决这一不足，并在研究验证和图书馆扩大方面实现一种新的范式。它以一种集成的、跨学科的方式将化学领域的学术研究和创造力与自动化的尖端工具结合在一起，包括微型设备开发和生物筛选。

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.