Strategies for Targeting and Isolating Cryptic Natural Products from Plants: Isolation and Structural Determination of piperholdripine and raduladioxanolide
Loading...
Authors
Burroughs, Megan
Issue Date
2024
Type
Dissertation
Language
en_US
Keywords
Natural Products
Alternative Title
Abstract
Archives of empirical data of medicinal herb usage can be found in ancient civilizations, but the start of the 19th century brought about the beginning of rational drug discovery from plants with Friedrich Sertürne's 1817 publication on the isolation, structure, and pharmaceutical effects of morphine. The so-called “waste" products of plants were sought after in the fields of medicine, agriculture, materials science, and ecological studies. This paper focuses on the strategies of isolation of “cryptic" natural products. Cryptic natural products represent a treasure trove of untapped potential. A cryptic natural product may be a minor component, only exist in certain individuals in a species, or require specific conditions to be generated. These specialized metabolites are often observed through their function or are hypothesized to exist based on the biosynthetic gene clusters. However, mining the genome of a multi-cellular organism, often on a cell-to-cell level, is an extremely difficult process. While other experiments focus on function, the actual isolation of a cryptic natural product, especially one that exists as a minor component or only functions in a synergistic system, can be difficult and time consuming. Chapter 2 focuses on the isolation of cryptic natural products through their function. Using 1H NMR resonance networking in correlation with bioactivity allows for the targeted isolation of bioactive metabolites. The structural information provided by the 1H NMR resonances allow for separations to be completed without a bioassay study at each step. This chapter describes using this method to isolate a novel cryptic natural product that shows high growth inhibition against S. cerevisiae. Chapter 3 demonstrates using untargeted metabolomic analysis to explore chemical heritability in Piper scintillans. A chemical heritability experiment requires the comparison of the chemical profiles of wild-type species. This chapter focuses on the annotation of the chemotype-defining masses. Chapter 4 offers proof that this untargeted/targeted method can lead to the isolation of a novel cryptic natural product. While these methods prove observing cryptic natural products can be accomplished, the isolation and full characterization can be difficult. Chapter 5 explores the potential of using single crystal x-ray diffraction to increase the rate of structure elucidation. The crystal sponge method and co-crystallization have potential to determine the absolute structure of hard to crystallize or liquid natural products. This chapter explores the methods, as well as future work to improve the chance of guest intake. Changing isolation strategies to increase the chance of isolated cryptic natural products is a common endeavor. These strategies use multivariate analysis to target compounds of interest, decreasing the amount of time and material necessary for isolation.