UCD Combinatorial Center - Novel and Diverse Pilot-Scal*

描述(由申请人提供)：为了响应RFA-RM-05-014，我们计划使用固相和溶液相策略来合成几个中试规模的文库，提交给NIH用于随后的各种生物分析。我们的目标是制备化学纯度高、结构多样的小分子化合物。这些小分子化合物将通过修改已公布的合成路线或酌情通过开发新的合成策略来制备。以多样性为导向的合成(DOS)文库通常有大约100-200个成员，每个成员的非商业小分子纯度=90%。我们的计划是为每个支架准备两种类型的库：(I)一个小型示范库，用于测试化学并验证程序，使用IRORI系统进行化合物合成和跟踪；(Ii)一个基于三叉戟或IRORI的库，以提供一个专注的化合物库。图书馆(I)和(II)的产出将被合并、存档，并供生化评估使用。二硝基二氟苯基支架的制备将会有更大的数量和数量。一些固相合成库将生成带有特定部位官能团的内置亲水手柄，以便这些化合物随后可以标记用于特定的分析，而另一些将在没有手柄的情况下制备。每一种化合物都将通过高效液相色谱进行纯度分析，并通过质谱学确认其身份。如果需要，将使用FlashTube先进的闪蒸层析法进行化合物纯化。NIH PubChem将用于管理我们的各种试点图书馆，我们计划建立一个带有PubChem链接的加州大学戴维斯分校组合化学网站。按照RFA的要求，每个图书馆成员至少有10毫克的档案，每个人的纯度=90%。

DESCRIPTION (provided by applicant): In response to the RFA-RM-05-014, we plan to use both solid- and solution-phase strategies to synthesize several pilot-scale libraries to be submitted to NIH for subsequent distribution for various biological assays. Our aim is to prepare chemically pure, structurally diverse small-molecule compounds. These small-molecule compounds will be prepared by adaptation of published synthetic routes or, as appropriate, by development of novel synthetic strategies. Diversity-oriented synthesis (DOS) libraries will generally have ~100-200 members each with =90% purity of non-commercial small-molecules. Our plan is to prepare two types of libraries for each scaffold: (i) a small demo library to test the chemistry and validate the procedures, using the IRORI system for compound synthesis and tracking; (ii) a Trident- or IRORI-based library to deliver a focused library of compounds. The output of libraries (i) and (ii) will be combined, archived, and made available for biochemical evaluation. The dinitrodifluorobenzene-based scaffold will be prepared in larger number and quantity. Some of the solid-phase synthesis libraries will be generated with a built-in hydrophilic handle with site-specific functional groups so that these compounds can be subsequently tagged for specific assays while others will be prepared without any handle. Each compound will be analyzed by HPLC for purity and its identity confirmed by mass spectroscopy. If needed, FlashTube advanced flash chromatography will be used for compound purification. The NIH PubChem will be used for management of our various pilot libraries and we plan to set up a UC Davis Combinatorial Chemistry web site with links to PubChem. As required by the RFA, at least 10 mg of each library member will be archived and each will have =90% purity.