Abstract: This dissertation describes two major studies directed toward: 1)
Thiophilic promoters for the direct transfer of resin-bound oligosaccharides to complex
acceptors in solid-phase organic synthesis, and 2) Studies toward development of
well-defined carbohydrate antigen-based S. pneumoniae vaccines. Chapter 1 provides some
background in glycoconjugate synthesis and glycorandomization. ... read moreChapter 2 explains
development of a method for the direct transfer of resin-bound glycans to complex
aglycones. This method has the potential to permit the rapid glycorandomization of natural
products through parallel synthesis. Chapter 3 and 4 provide details on my synthetic works
on a multi-investigator project focused on developing a new approach to non-proteinogenic
oligosaccharide-based vaccines. In this approach, the antigen is directly attached to a
small molecule toll-like receptor agonist. By eliminating the need for adjuvants, this
approach is anticipated to greatly reduce unwanted inflammatory responses commonly
associated with many types of vaccines. The synthesis of three generations of carbohydrate
toll-like-receptor (TLR) 7 agonist conjugate vaccine candidates will be
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Chemistry.
Advisor: Clay Bennett.
Committee: Krishna Kumar, Samuel Thomas, and Isaac Krauss.