Biomimetic Seleninates and Selenonates

摘要

Aliphatic seleninic (RSeO_2H) and selenonic (RSeO_3H) acids and their salts may be viewed as isosteres of the biologically ubiquitous anionic O-phosphate, O-sulfate, and carboxylate groups and can be predicted to resist the action of most enzymes that operate in the biosynthesis or subsequent processing of those bioanions. While sometimes considered too unstable or too toxic for medicinal chemistry use, seleninates and selenonates nevertheless exhibit unique reactivity that can potentially be channeled for an assortment of bioorganic applications, including studies of enzyme action and inhibition, enzyme structure and mechanism, and biomimetic chemical ligation. We report a mild and efficient method for the preparation of pyranose-, nucleoside-, amino acid-, and polyhydric-based seleninates and selenonates, as well as some unusual coupling reactions with nucleophilic functionality that is commonly found in proteins and enzyme active sites.