Synthesis of biologically important C-glycoinositols
Item
-
Title
-
Synthesis of biologically important C-glycoinositols
-
Identifier
-
d_2009_2013:925e8acefccf:09991
-
identifier
-
10142
-
Creator
-
Hans, Sunej,
-
Contributor
-
David R. Mootoo
-
Date
-
2009
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Organic chemistry
-
Abstract
-
Glycosylinositol subunits comprise important glycoproteins on eurkayotic cell membranes and oligosaccharide components of the cell wall of mycobacteria. Glycosylinositols are also believed to function as secondary messengers in cellular processes, such as the mediation of insulin action. Analogues of glycoinositols in which the ring or glycosidic oxygen of the acetal residue is replaced with a methylene group (C- and carba-glycoside respectively), have attracted interest as mechanistic probes because of their greater hydrolytic stability and different conformational behavior compared with the native O-glycosides.;Chapter 1 of this thesis presents an overview of selected biologically important glycoinositols, and of previous synthetic approaches to C- and carba-glycosides. Chapters 2, 3 and 4 describes the synthesis of the C-glycosides of 6-O-(alpha-mannosyl)-myo-inositol and 4-O-(2-amino-2-deoxy-beta-D-galactopyranosyl)-3- O-methyl-D-chiro-inositol (also called INS-2), and the carba-glycoside of INS-2.;The synthetic strategy for these complex C- and carba-glycosides centers on formulation of the "sugar" or "glycone" component from a highly oxygenated cyclic enol ether in which the enolic oxygen is endo- or exo-cyclic, respectively. A key innovative element in these syntheses is an oxocarbenium ion cyclization strategy wherein these enol ethers are produced with complete stereocontrol from highly substituted thioacetal-enol ether precursors. An appealing aspect of this plan is that the cyclization precursors may be accessed in a convergent fashion starting from the esterification of "glycone" and "aglycone" components, thereby allowing for the preparation of a variety of C- or carba-inositols with different sugar and inositol residues.
-
Type
-
dissertation
-
Source
-
2009_2013.csv
-
degree
-
Ph.D.
-
Program
-
Chemistry
