Synthesis of C-Glycosides via Anodic Olefin Coupling Reaction and Building of Addressable C-Glycoside Libraries on Microelectrode Arrays
Date of Award
Doctor of Philosophy (PhD)
Microelectrode array based small molecule microarrays provide a real-time, label-free method to probe bindings of small molecules with their biological receptors. We plan to extend our efforts in building small molecular microelectrode arrays to the placement of C-glycoside derivatives on a microelectrode array, as C-glycosides may show novel properties different from their N- and O-glycoside counterparts.
Anodic olefin coupling reaction has been shown to be a powerful method for contructing 5-membered ring tetraphydrofuran and 6-membered ring tetrahydropyran structures. In Chapter 3, a rapid, two-step procedure (Wittig reaction - anodic olefin coupling) has been developed for converting sugar derivatives into C-glycosides containing a masked aldehyde functional group. For furanose derivatives, both the enol ether substrates and vinyl sulfide substrates formed the cyclized products after anodic oxidation. For pyranose derivatives, vinyl sulfide substrates were necessary to accelerate the cyclization of the radical cation intermediates. During the investigation process, it was found that electrolyte, solvent combination, and substrate polarity all play roles in the experimental results. Selective deprotection of the acetal groups and further manipulations of the substrates were also performed in this Chapter.
In Chapter 4, a Diels-Alder strategy and a Cu(I)-catalyzed coupling strategy have been developed to site-selectively place C-glycosides onto microelectrode arrays. In practice, the Cu(I) strategy requires less substrate modification thus is more convenient, while the Diels-Alder strategy provides a complementary methodology. In the process of substrate modification, it was found that the steric hindrance of the C-glycoside substrates needed special consideration. Moreover, the C-glycoside microelectrode arrays have demonstrated their ability in biological evaluations by successfully performing electrochemical signaling when binding with streptavidin.
Chair and Committee
Kevin D Moeller
Vladimir B Birman, John-Stephen A Taylor, Sophia E Hayes, Garland R Marshall, James W Janetka
Xu, Guoxi, "Synthesis of C-Glycosides via Anodic Olefin Coupling Reaction and Building of Addressable C-Glycoside Libraries on Microelectrode Arrays" (2012). Arts & Sciences Electronic Theses and Dissertations. 167.