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

描述（由申请人提供）：该化学方法和文库开发卓越中心的总体目标是基于在新型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）等领域开展的原始研究，生成新的化学文库。我们的项目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平行有机合成的微反应器，并发现用于液相色谱的新的手性固定相。每个项目分为研究和应用两个阶段。在研究阶段，将在个别研究小组中发展新的方法。在开发阶段，一个集中的设施，多样性导向合成（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，并为项目提供效用和实用性的即时“真实世界”反馈。严格的质量控制将确保高纯度的样品将与生物领域的合作者共享。该化合物库预计最终将由10-20毫克的5万个结构多样的样品组成，也将向工业界和学术界的外部人士开放。虽然学术实验室已经开发了许多新的图书馆合成方法，并对图书馆生产和分析的高效自动化做出了重要贡献，但他们在实际生产图书馆和使非专业实验室可以访问图书馆方面还存在不足。我们的中心计划将解决这一不足，并实现研究验证和图书馆规模扩大的新范式。它将化学领域的学术研究和创造力与合成、分析和分离方面的尖端自动化工具结合在一起，以综合的、跨学科的方式，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.