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BORONIC ACID SYNTHESIS
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This research will explore the synthesis of a new class of compounds, boronic acid analogs of nucleoside monophosphates. The goal of this research is to evaluate the possibility of using a boronic acid moiety as a replacement for phosphate and phosphonate groups. The initial targets include analogs of AMP, dAMP, CMP, dCMP, tenofovir, and adefovir as illustrated in Figure 1. These compounds will then be examined for usefulness as antiviral agents. A synthesis applicable to a series of these compounds is under development.
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 Figure 1: Lead compounds and proposed boronic acid analogs. |
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Upon the completion of the syntheses, the stability and physical properties of these analogs will be determined. Then, these boronic acid-containing compounds will be tested and characterized as inhibitors and/or substrates of various viral and cellular kinases and DNA polymerases. The formation of a boronic-phosphoric mixed anhydride linkage via enzymatic and chemical reactions will be explored. If this linkage forms and is stable, these compounds will also be studied.
In summary, this research will develop a new class of compounds and evaluate their usefulness as antiviral chemotherapies. The development of new antivirals is of vital importance to public health as new viral diseases are continuously being discovered and known viruses develop resistance to existing agents. |