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: 8337256
• 负责人: Peter Wipf
• 金额: $ 137.05万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8337256
• 关键词: 3-Dimensional; Address; Applications Grants; Area; 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（申请人提供）：化学方法学和库开发卓越中心的总体目标是基于在新型肽模拟物的合成和分析领域进行的原始研究产生新型化学库（项目1），多样性导向的合成和战略分离的创新方法相结合（项目2），氟聚合物基微反应器的开发和实施（项目3）。我们的计划将开发使用氟相合成策略的新分离技术，设计和开发用于纳米级高度平行有机合成的微反应器，并发现用于液相色谱的新手性固定相。每个项目都有两个阶段：研究和应用。在研究阶段，各个研究小组将制定新的方法。在开发阶段，一个集中的设施，多样性导向的合成（DOS）核心，方便地访问最先进的自动化合成，分离和分析设备，将验证协议和放大库合成访问500- 10，000单一化合物每个库。这一安排将为所有新方法提供真正独立的验证，并为项目提供关于实用性和实用性的即时“真实的世界”反馈。严格的质量控制将确保与生物领域的合作者共享高纯度样品。该化合物库预计最终将由10-20 mg数量的> 50，000个结构多样的样品组成，也将向来自工业和制药业的外部各方提供。虽然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的有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非专业实验室能够访问图书馆方面却做得不够。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规模扩大的新范式。它结合了学术研究和化学创造力的力量与合成，分析和分离自动化的尖端工具，以综合，跨学科的方式，包括微尺度设备开发和生物筛选。

项目成果

Mitochondria as a target in treatment.

• DOI: 10.1002/em.20554
• 发表时间: 2010-06
• 期刊: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
• 影响因子: 2.8
• 作者: Frantz, Marie-Celine;Wipf, Peter
• 通讯作者: Wipf, Peter

Synthesis of 1,2,4-triazines and the triazinoisoquinolinedione DEF ring system of noelaquinone.

• DOI: 10.1039/c2ob25353d
• 发表时间: 2012-08-14
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Cao L;Maciejewski JP;Elzner S;Amantini D;Wipf P
• 通讯作者: Wipf P

Multicomponent synthesis of alpha-branched amides.

• DOI: 10.1021/ol802764j
• 发表时间: 2009-02-19
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: DeBenedetto MV;Green ME;Wan S;Park JH;Floreancig PE
• 通讯作者: Floreancig PE

Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation.

• DOI: 10.1021/jm3017464
• 发表时间: 2013-03-14
• 期刊: JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 7.3
• 作者: Yang, Peng;Wang, Lipinig;Peng, Rentian;Almehizia, Abdulrahman A.;Tong, Qin;Myint, Kyaw-Zeyar;Ouyang, Qin;Alqarni, Mohammed Hamed;Wang, Lirong;Xie, Xiang-Qun
• 通讯作者: Xie, Xiang-Qun

Synthesis of the Naturally Occurring (-)-1,3,5-Tri-O-Caffeoylquinic Acid.

• DOI: 10.1055/s-0029-1217183
• 发表时间: 2009-02-11
• 期刊: Synlett : accounts and rapid communications in synthetic organic chemistry
• 作者: Brummond KM;Deforrest JE
• 通讯作者: Deforrest JE