Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties
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A series of novel glycopyranosyl azides were synthesized wherein the carbohydrate moiety was peracylated with four acetyl, propionyl, butanoyl, pentanoyl (valeryl) or 3-methylbutanoyl (isovaleryl) ester linked groups. A panel of glycoconjugates was synthesized from these glycopyranosyl azides using copper-catalyzed azide-alkyne cycloaddn. The in vitro metabolic stability, plasma stability and plasma protein binding was then measured to establish the impact of the different acyl group when presented on a common scaffold. The acetyl, propionyl and butanoyl esters exhibited metab. consistent with esterase processing, and various mono-, di- and tri-acylated hydrolysis products as well as the fully hydrolyzed compd. were detected. In contrast, the pentanoyl and 3-methylbutanoyl esters were stable.
Bioorganic & Medicinal Chemistry Letters
© 2013 Elsevier. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
Biologically Active Molecules