Document Type


Date of Award

Spring 5-31-2012

Degree Name

Master of Science in Pharmaceutical Chemistry - (M.S.)


Chemistry and Environmental Science

First Advisor

Haidong Huang

Second Advisor

Carol A. Venanzi

Third Advisor

Tamara M. Gund

Fourth Advisor

Edgardo Tabion Farinas


S-Adenosyl-L-Methionine (SAM), which is involved in methyl group transfers, is the second most abundant coenzyme in the human body. It is made from adenosinetriphosphate (ATP) and methionine catalyzed by adenosyltransferase. Methyltransferases (MTs) transfer the activated methyl group from the sulfur center to a specific position in a variety of substrates, e.g., DNA, RNA, proteins, and secondary metabolites. Methyltransferases have been linked to various diseases, including cancer.

In recent years, more and more SAM analogues have been reported. These analogues show activities in biological target labeling. The purpose of this thesis is to design and synthesize new SAM analogues to inhibit cytosine DNA Methyltransferases in tumor cells. A series of target compounds was designed and synthesized in several steps from the starting material adenosine. The synthesis route has been divided into three parts: introduction of the nitrogen at the 5’ position, synthesis of aromatic aldehyde, and connection of these two compounds. More compounds with the same core structure will be designed and synthesized. The inhibition activities will be tested in future studies.