Development and application of NMR spectroscopy to marine natural products structure and biosynthesis

This thesis is broken into three major research foci. The first project deals with the biosynthesis of cyclomarin A and these efforts are detailed in chapter II. The second area of pursuit was the development of new NMR experiments to aid in the structure elucidation of natural products. These efforts are outlined in chapters III–VIII. Chapter III describes the development and application of an experiment to aid in the structure elucidation of peptide type natural products by sorting their homonuclear spin systems by the heteronuclear chemical shift of the natural isotopic abundance amide nitrogens. The next chapter also deals with the detection of 15N. In this chapter, a method describing the rapid and efficient detection of intact 15 N-13C units in biosynthetic studies are presented. Chapter V describes a new method for the detection of homonuclear coupling constants from higher order, degenerate, or symmetric spin systems. Following this, two methods for the determination of long-range heteronuclear coupling constants are presented in chapters VI and VII. The eighth chapter describes the use of diffusion edited NMR spectra to deconvolute natural products mixtures. These experiments should also find wide application in other areas such as combinatorial chemistry and the study of protein-ligand binding. The third theme of this thesis deals with projects involving natural products structure elucidation. The structure elucidation of the taveuniamides and phormidolide integrate time honored bioassay guided fractionation with new powerful NMR techniques to solve the planar and stereochemical structures of the isolated compounds; this is described in chapters VIII and IX, respectively.