Synthesis of caryophyllose-containing lipooligosaccharides from Mycobacterium marinum

• Author / Creator

  Chu, Chun-Jui

• “To understand something” is a perpetual theme in scientific research. In carbohydrate chemistry, we pursue to understand certain properties of sugar molecules. This is further described as the purpose of my research “understanding Mycobacterium marinum lipooligosaccharides’ (LOSs) immnuogenic properties on a molecular level.”
  To start addressing this goal, LOSs from M. marinum have to be synthesized because they could not be isolated in pure and abundant quantity. These species are found in nature as a heterogeneous mixture of four major compounds, named LOS-I–IV, which all share LOS-I as a common structural motif. LOS-I is a pentasaccharide that contains a trehalose core with three hydroxyl groups acylated with fatty acids. In LOS-II and LOS-III, this pentasacccharide is modified by the addition of one or two residues of a rare branched monosaccharide, caryophyllose. LOS-IV consists of LOS-III further functionalized with a terminal N-acyl-D-fucosyl moiety.
  This thesis describes my work focused on synthesizing M. marinum LOS I–IV. I will first discuss my studies on preparing the common triacylated trehalose core, which could be prepared by glycosylation between two glucose moieties and then acylation with synthesized, optically-pure lipids. Next, I outline my attempts to synthesize caryophyllose, which was hindered by a low- yielding key carbon–carbon bond formation step. This made the synthesis of LOS-II–IV not possible at this stage; however, my work suggested a better plan for the future. Finally, I will report the synthesis of a protected derivative of LOS-I, starting from the triacylated trehalose core, via its coupling with different glycosyl fluorides to give the pentasaccharide backbone. Unfortunately, the final deprotection was unsuccessful and thus the synthesis of LOS-I was not achieved. This led me to propose an alternate plan for synthesizing LOS-I and the remaining targets.

• Subjects / Keywords

  • lipooligosaccharides
  • mycobacterium
  • synthesis

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-mgea-an80

• License

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