SYNTHESIS OF CONJUGATES OF L-FUCOSE AND ORTHO-CARBORANE AS POTENTIAL AGENTS FOR BORON NEUTRON CAPTURE THERAPY AND SYNTHESIS OF 2,3-DIDEOXY-2,3-METHANORIBOFURANOSIDE GLYCOSYL DONORS AND A STUDY OF THEIR USE IN STEREOCONTROLLED GLYCOSYLATION REACTIONS
This dissertation comprises of two projects: Project I describes the synthesis of conjugates of L-fucose and ortho-carborane as potential agents for Boron Neutron Capture Therapy. Boron Neutron Capture Therapy (BNCT) is a form of binary cancer therapy that proposes the destruction of cancer cells by compounds decorated with boron atoms. When such cells are irradiated with slow moving (thermal) neutrons, a nuclear reaction generates localized high-energy gamma radiation along with very short-lived Helium and Lithium ions that destroy them completely without affecting the neighboring healthy cells. The challenge however lies in selective delivery of boron atoms to cancer cells in presence of the normal ones. L-fucose, a building block of glycolipids and glycopeptides is over-expressed in tumor cells and therefore might serve as a boron-carrying vehicle to such cells selectively. Project II describes the synthesis of 2,3-dideoxy-2,3-methanoribofuranoside glycosyl donors and a study of their use in streocontrolled glycosylation reactions. Synthesis of 1,2-cis-beta-glycoside bonds has posed a constant challenge to synthetic chemists. Even though a number of methodologies have been reported, very few of these have been applied to a furanose ring system to form a 1,2-cis-beta-glycoside bond with excellent stereocontrol. Recently, Lowary and co-workers have reported the synthesis of such a bond in a 5-membered furanose ring system with excellent stereoselectivity. In their report, the researchers have shown that when furanosyl donors with a fused 2,3-epoxy ring are subjected to glycosylation reactions, the acceptor alcohol stereoselectively forms the glycoside bond from the same face of the furanose ring as that occupied by the epoxy group, even though the result is a sterically congested product. One reason behind this stereoselectivity could be the directing effect of a hydrogen bond between epoxide oxygen and the incoming nucleophile. This project investigates such possibility by substituting the epoxide with a cyclopropyl analog which cannot form such hydrogen bonds. Upon glycosylation, this modified donor preferred a glycoside bond on the side opposite to the cyclopropyl group, i.e., the sterically less congested glycoside was the major product. Thus, the formation of a hydrogen bond between epoxy oxygen and acceptor might play an important role in glycosylation reactions with epoxy-donors.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:conjugates of l fucose and ortho carborane potential agents boron neutron capture therapy 2 3 dideoxy methanoribofuranoside glycosyl donors stereocontrolled glycosylation reactions
Date of Publication:01/01/2003