Title

Synthesis of organic compounds to model biological systems.

Date of Award

5-1-2016

Document Type

Thesis

School

College of Liberal Arts

Degree Name

Bachelor in Arts

Abstract

Biological systems are composed of large mcro-molecules that are responsible for the regulatory functions in the cell. These systems are important in order to learn about how the cell works and how it repairs itself. Additionally, these macromolecules are often used in industrial applications. Some of the research done on biological systems uses small molecules to study these macro-molecules. Small organic molecules can be synthesized and used to mimic the biological system of interest to learn about its stability, or its mechanistic pathway as well as other important aspects. Surface salt bridge interactions are non-covalent interactions that are formed between two oppositely charged residues. The strength of surface salt bridges are still contentious regarding their contributions to the stability of a protein. During the course of this project, we sought to synthesize a biphenyl derivative, which mimics a solvent exposed salt bridge interaction, to measure the strength of this type of interaction present in protein. 2-Bromoxylene-m-xylene was converted to a diacid, then to a diester, then to a monoacid. 3-Hydroxypropionitrile was oxidized and then the addition of a protecting group was added to the alcohol. Once the final target molecule is isolated, the strength of the surface salt bridge interaction will be measured using NMR. Another project where a small molecule approach may be helpful is in phosphorodithioates. Phosphorodithioates are modified oligonucleotides that are used to study phosphodiester cleavage. Phosphodiester cleavage happens relatively slowly, but can be catalyzed by a divalent metal ion. The mechanism for phosphodiester cleavage, and in particular the mechanism of metal-ion catalysis, is still the subject of much investigation. In this project, we sought to synthesize 5'Uridine 3' Guanidine phosphorodithioate dinucleotide, (UPS-b2-sG), in order to use this molecule for kinetic studies and determine the role of metal ions in phosphodiester cleavage. The compound that has been successfully synthesized thus far is the phosphorothioamidite intermediate, with a 75.22% crude yield. An automated solid synthesizer, which would usually be used for such a synthesis was not available and thus a modified strategy was developed using a centrifuge tube. Once the phosphorodithioate dinucleotide has been synthesized, the Cassano lab will use this molecule to study whether phosphodiester cleavage occurs at the same rate as the -oxo analogue.