University of Pittsburgh Center for Chemical Diversity

化学方法卓越中心和图书馆发展基金的总体目标

The overall goal of this Center of Excellence in Chemical Methodologies and LibraryDevelopment grant applicationis to generate novel chemical librariesbased on originalresearch carried out in the areas of synthesisand analysis of novel peptidemimetics (Project 1), the combinationof innovativemethodsfor diversity-orientedsynthesis and strategicseparations (Project 2), and the developmentand implementation of fluoropolymer-based microreactors(Project 3). Our Programwill develop new separationtechnologies usingfluorous phase synthesisstrategies, design and develop microreactorsfor nano-scale highly parallel organicsynthesis, and discover new chiralstationary phases for liquidphase chromatography. Each Project has two stages: research and application. At the research stage, new methodologieswill be developed in individualresearch groups. At the development stage, a centralized facility, the Diversity-OrientedSynthesis (DOS) Core with convenient access to state-of-the-art automated synthesis,separation, and analysis equipment, will validate the protocolsand scale-up library synthesisto access 500-10,000 singlecompounds per library. This arrangement will provide trulyindependent validationfor all new methodologiesand provide the Projectswith immediate "real world" feedback of utilityand practicality. Rigorousquality controlwill ensure high purity samples that will be shared with collaborators inthe biologicalfields. This Compound Library, envisionedto be composed of ultimately>50,000 structurallydiverse samples in 10-20 mg quantities,will also be accessible to outsidepartiesfrom industry and academe. While academic labs have developed many new methodsfor library synthesisand contributedimportant insightstoward efficient automation for library productionand analysis, they have fallen short in actually producinglibrariesand making them accessibleto non-specialized labs. Our Center Programwill address this deficiencyand realize a new paradigm in research validationand library scale-up. It combinesthe power of academic research and creativityin Chemistry with cutting-edgetools of automation in synthesis, analysis, and separation in an integrated, interdisciplinarymanner that includesmicroscaledevice developmentand biologicalscreening.