Carl Jones and Dr. Matt A. Peterson, Chemistry

We have made significant progress toward the synthesis of one branch of the library of compounds that we plan to synthesize. The scheme we have followed is shown below. Once synthesized, we plan to have the compounds tested by expert collaborators to see how well they bind HTLV integrase. In addition, they will be tested against many viruses and cancers, as well as HIV. Because they are nucleoside based, it is impossible to predict exactly what type of biological activity these compounds will have. They could possibly treat a variety of diseases.

The first set of reactions went as predicted. Moving from compounds 18 to 19, however, proved to be extremely difficult. After several attempts, we were able to find the necessary concentration of solvent to allow the reaction to proceed. Now we are able to synthesize the product at a rate of about 1 gram per week. Compounds 20-22 are entirely new compounds that have never before been characterized, and are important intermediates to our final goal. Being new syntheses, however, we have also had to adjust conditions several times to isolate the pure product repeatedly in high yields at each of those steps.

By May of 2005 we expect to have some of the desired compounds completed and ready for biological testing. A new graduate student in the lab will most likely speed the process. Once the results come back, we will have some idea of how well the compounds bind HIV integrase, and hopefully what interactions make them bind. That way, we can adjust future compounds based on the knowledge gained from biological testing.