Adaptations and methodologies for enhanced identification of lead compounds

实施了一个程序来预压裂天然产物库中提取物的一个大子集。这一举措产生了大量的预分馏样品（18，000），更适合我们实验室从事的高通量天然产物发现工作。我们构建的提取物预分离库为在各种不同的检测系统中增强铅的鉴定提供了高价值的筛选资源，我们还专注于扩展我们的纯天然产物库，因为这为筛选提取物相关的问题提供了理想的解决方案。提高我们的结构解析能力的方法是该项目的另一个重点，特别强调用于分配未知天然产物的相对和绝对构型的技术。一些具有挑战性的立体化学测定所取得的小组采用不同的方法，包括水解，衍生化，液相色谱-质谱分析，核磁共振（NMR）数据库比较，和圆二色性（CD）的研究。一种新的海绵衍生的磷大环内酯的完整结构解析，利用微尺度手性衍生化和化学互变的组合，与NMR和CD分析。

A program was implemented to prefractionate a large subset of extracts from the Natural Products Repository. This initiative has generated a substantial collection of prefractionated samples (18,000) that are more suited for the high-throughput natural products discovery efforts our laboratory is engaged in. The extract prefractionation library we constructed provides a high-value screening resource for enhanced lead identification in a variety of different assay systems.We have also focused on expansion of our pure natural products library, since this provides the ideal solution to the problems associated with screening extracts. Methods to enhance our structural elucidation capabilities are another major focus of this project, with a special emphasis on techniques used to assign the relative and absolute configuration of unknown natural products. Some of the challenging stereochemical determinations achieved by the group employed diverse methodologies including hydrolysis, derivatization, and liquid chromatography-mass spectrometry analyses, nuclear magnetic resonance (NMR) database comparisons, and circular dichroism (CD) studies. The complete structural elucidation of a novel sponge-derived phosphomacrolide, utilized a combination of micro-scale chiral derivatization and chemical interconversion, with NMR and CD analyses.