Tackling the glycosylation of 2-deoxy-sugars: A reagent-controlled approach utilizing cyclopropenium cations for the α-selective glycosylations of 2-deoxy-, 2,6-dideoxy- and 2,3,6-trideoxy-sugars
Abstract: Gaining access to stereodefined deoxy-sugar containing
oligosaccharides, such as those containing 2,6-dideoxy and 2,3,6-trideoxy motifs, remains a
formidable challenge. This is largely due to the difficulties associated with controlling
the selectivity of glycosylations using deoxy-sugar donors. Herein, the development of
three generations of reagent-controlled approaches utilizing ... read morecyclopropenium cations are
described. Chapter 2 describes our first-generation approach which utilized a
3,3-dichloro-1,2-diphenylcyclopropene/tetrabutylammonium iodide (TBAI) promoter system for
α-selective glycosylations. These substrates reacted with a range of glycosyl acceptors to
afford products in 55 to 99% yield, with selectivities ranging from 3:1 α:β to all α,
determined by NMR. In chapter 3 we describe how we improved upon the method by utilizing a
3,3-dibromo-1,2-diphenylcyclopropenone/TBAI system. This latter system activated
deoxy-sugar donors to react with a range of glycosyl acceptors to afford products within 50
to 98% yield, with selectivities ranging from 8:1 α:β to all α. Chapter 4 describes our
studies to improve the synthetic utility and substrate scope of the reaction and eliminate
the need for TBAI. In these studies we found that activating 2-deoxy-hemiacetal donors with
2,3-bis(2,3,4-trimethoxyphenyl)cyclopropenone/oxalyl bromide or
2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione/oxalyl bromide can also induce
α-selective glycosylations without the need for TBAI. These latter activating agents are
much faster and higher yielding then our initial approaches, reacting with a range of
glycosyl donors and acceptors to afford products within 53 to 74% yield, with selectivities
ranging from 6:1 α:β to all α. Most importantly, it allows for the glycosylations for the
highly reactive and acid sensitive 2,3,6-trideoxy sugar L-rhodinose, an important
structural motif in various carbohydrate based natural products.
Thesis (Ph.D.)--Tufts University, 2016.
Submitted to the Dept. of Chemistry.
Advisor: Clay Bennett.
Committee: Samuel Thomas, Krishna Kumar, and George O'Doherty.
Keywords: Organic chemistry, and Chemistry.read less