A new approach to the synthesis of glycosylated small molecule compound libraries has been developed. The approach, termed Post Glycosylation Diversification (PGD), utilizes functionalized aglycones on deprotected sugar scaffolds to generate library compounds using established transformations. The use of unprotected, advanced intermediate, glycosides offers an advantage over other techniques for accessing glycosylated libraries, such as glycorandomization or neoglycorandomization. PGD is able to generate final compounds, which are applicable to SAR type experiments in a rapid fashion from advanced intermediates. To showcase the method, we synthesized a collection of compounds based on the amino sugar desosamine from erythromycin. Aglycones of PGD precursors were derivatized by click, Suzuki, and acylation reactions. New compounds were then evaluated in transcription/translation assays. We have extended this technique to other amino sugars, such as kanosamine, and in the process also developed a means of accessing mono-, di-, and mixed alkyl derivatives of such, and incorporated these sugars into novel Kanamycin B derivatives.

Post glycosylation diversification (PGD), a new approach to the synthesis of glycosylated small molecule compound libraries, and its application towards novel bioactive compounds containing amino sugars

256th National Meeting (2018)

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