Adaptations and methodologies for enhanced identification of lead compounds

实现了一个程序来预分离天然产物库中提取物的大子集。这一举措产生了大量的预分离样品（18,000），这些样品更适合我们实验室所从事的高通量天然产物发现工作。我们构建的萃取物预分离文库为在各种不同的测定系统中加强铅的鉴定提供了高价值的筛选资源。我们还专注于扩大我们的纯天然产品库，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这个项目的另一个主要焦点，特别强调用于分配未知天然产物的相对和绝对结构的技术。该小组完成的一些具有挑战性的立体化学测定采用了多种方法，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）研究。利用微尺度手性衍生化和化学相互转化，结合核磁共振和CD分析，对一种新型海绵衍生的磷酸丙烯内酯进行了完整的结构解析。

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.