Kirk Wyatt

Synthesis of Potential Protein Tyrosine Kinase Inhibitors

My S3 project involves the synthesis of 3-aminoquinazolinone and 2'-deoxyguanosine derivatives as potential protein tyrosine kinase (PTK) inhibitors. PTK inhibitors are of important significance because of their ability to act as anticancer agents.

The 3-aminoquinazolinone derivatives were formed by reaction with aldehydes to form imines and with acid chlorides to form amides. In all, eleven 3-aminoquinazolinone derivatives were synthesized.

Before synthesis of the 2'-deoxyguanosine derivatives, the hydroxyl groups of the sugar moiety first had to be protected (this was accomplished with the tert-butyl dimethyl silyl protecting group) and then a sulfonate had to be introduced at the O6 position. Once the sulfonate had been introduced, its displacement by amines and alcohols gave the desired products which were purified via chromatographic methods. The protection and sulfonation of 2'-deoxyguanosine has been achieved on a large-scale, and the synthesis of the O6-substituted 2'-deoxyguanosine analogs is well underway. The inhibition studies which will determine the activities of the compounds with the target kinases will be done within the coming weeks.

Faculty Mentors: Laurie Witucki and Felix Ngassa

UPDATE:

Kirk presented at the 237th National Meeting of the American Chemical Society March 2009 in Salt Lake City, UT.

Page last modified January 21, 2011