Microscale structure determination of biologically active natural products

Structure determination plays a very important role in natural product chemistry. Absolute configurational assignment is crucial for the understanding of structure-activity relationships between ligand and receptors. Recently a great deal of effort has been made in applying CD spectroscopic methods in microscale structure determination of natural products. Five successful examples are presented in this thesis.; Chapter I briefly describes the exciton coupled circular dichroism method.; Chapter II includes two parts. In Part 1, the absolute stereochemistry of two bacteriohopanepentols are determined by the bichromophoric CD method on a microgram scale. Part 2 presents a chiroptical/chemical strategy for the configurational assignment of acyclic 1,3-polyols by combining the bichromophoric CD method with a stereospecific ketalization method. A divergent synthesis was used to prepare model acyclic 1,3-polyols. The absolute configurations of model 1,3-polyols were quickly assigned based on the combination of CD spectra and the synthetic approach.; Chapter III is a further application of bichromophoric CD method to sphingosines, which are breakdown products of various sphingolipids. By using two strong fluorescent chromophores (N-naphthimido and 2-naphthoate), all possible stereoisomers of sphingosines were distinguished. Such structural analysis can be carried out at a level of ca. 1 microgram.; Chapter IV describes the extension of the exciton chirality method to tertiary amine containing compounds by novel chromophoric derivatization through quaternary salt formation.; Chapter V describes the course of characterizing two unknown ouabain isomers from mammalian sources: HIF from bovine hypothalamus and OLC from human plasma. Both are strong Na{dollar}sp+{dollar}/K{dollar}sp+{dollar}-ATPase inhibitors. Challenged by the nanogram amounts of available samples, a combined microscale derivatization/HPLC/CD spectroscopy method was developed for structural comparisons among HIF, OLC, and ouabain.