Adaptations and methodologies for enhanced identification of lead compounds

实施了一项计划，从天然产物储存库中预分取一大部分提取物。这一倡议产生了大量的预分馏样品(18,000个)，这些样品更适合我们实验室从事的高通量天然产品发现工作。我们构建的提取物预分解库为在各种不同的检测系统中加强铅的鉴定提供了一个高价值的筛选资源。我们还专注于扩大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。增强我们的结构解释能力的方法是这个项目的另一个主要重点，特别强调用于指定未知天然产物的相对和绝对构型的技术。该小组完成的一些具有挑战性的立体化学测定采用了不同的方法，包括水解、衍生化和液-质联用分析、核磁共振数据库比较和圆二色谱(CD)研究。利用微尺度手性衍生化和化学相互转化相结合的方法，结合核磁共振和圆二色谱分析，对一种新型海绵衍生的磷大内酯进行了完整的结构鉴定。

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.