Towards the Synthesis of Boronated Amino Acid Analogs: Precursors for Novel HIV-1 Protease Inhibitors
Document Type
Oral Presentation
Campus where you would like to present
SURC 137B
Start Date
17-5-2012
End Date
17-5-2012
Abstract
A class of HIV drugs called protease inhibitors have proven effective in slowing progression of the disease. This research aims to create two boronated amino acid analogs that will later be incorporated into potential HIV-1 protease inhibitors. These structures have been designed to decrease toxic exposure to patients and aim to increase bioavailability, allowing for more effective uptake and smaller required dosages. To synthesize the analogs, boronic acids were coupled with the protecting group (1R,2R)-dicyclohexyl-1,2-ethanediol (DICHED), which also served as a chiral director giving the product correct stereospecificity for biological activity. The product was homologated using butyllithium and dichloromethane to insert a new chiral chlorinated carbon between the R group and boron. In an SN2 reaction the chlorine was substituted for hexamethyldisilazane, which contains nitrogen and creates the analog amino group. The product was desilylated using methanol and immediately acylated with acetic anhydride and acetic acid. DICHED was removed and exchanged for two hydroxyl groups using phenyl boronic acid to yield the boronated amino acid analog. In the future, the boronated amino acid analogs will be coupled with tripeptides to create potential HIV-1 protease inhibitors.
Recommended Citation
Faulkner, Andrea, "Towards the Synthesis of Boronated Amino Acid Analogs: Precursors for Novel HIV-1 Protease Inhibitors" (2012). Symposium Of University Research and Creative Expression (SOURCE). 112.
https://digitalcommons.cwu.edu/source/2012/oralpresentations/112
Additional Mentoring Department
Chemistry
Towards the Synthesis of Boronated Amino Acid Analogs: Precursors for Novel HIV-1 Protease Inhibitors
SURC 137B
A class of HIV drugs called protease inhibitors have proven effective in slowing progression of the disease. This research aims to create two boronated amino acid analogs that will later be incorporated into potential HIV-1 protease inhibitors. These structures have been designed to decrease toxic exposure to patients and aim to increase bioavailability, allowing for more effective uptake and smaller required dosages. To synthesize the analogs, boronic acids were coupled with the protecting group (1R,2R)-dicyclohexyl-1,2-ethanediol (DICHED), which also served as a chiral director giving the product correct stereospecificity for biological activity. The product was homologated using butyllithium and dichloromethane to insert a new chiral chlorinated carbon between the R group and boron. In an SN2 reaction the chlorine was substituted for hexamethyldisilazane, which contains nitrogen and creates the analog amino group. The product was desilylated using methanol and immediately acylated with acetic anhydride and acetic acid. DICHED was removed and exchanged for two hydroxyl groups using phenyl boronic acid to yield the boronated amino acid analog. In the future, the boronated amino acid analogs will be coupled with tripeptides to create potential HIV-1 protease inhibitors.
Faculty Mentor(s)
Levente Fabry-Asztalos