Synthesis of aminooxy and N-alkylaminooxy amines for use in bioconjugation.

Five Boc-protected aminooxy and N-alkylaminooxy amines have been synthesized in 60-95% overall yield using a common synthetic strategy from readily available two- and three-carbon Cbz-protected amino alcohols. The amines can be linked to biomolecules via amide formation and incorporated directly into peptoids via submonomer synthesis. Subsequent deprotection of the aminooxy and N-alkylaminooxy groups enables conjugation with desired target molecules via established chemoselective ligation methods. The range of derivatives synthesized allows different distances to be established between the conjugated molecules.

Chemoselective and microwave-assisted synthesis of glycopeptoids.

The chemoselective glycosylation of N-alkylaminooxy side chains with unprotected reducing sugars has proven useful for the synthesis of glycopeptides. Herein, we extend the N-alkylaminooxy strategy to the synthesis of glycopeptoids. A N-methylaminooxy submonomer was efficiently synthesized and incorporated into peptoids. Glycosylation of the peptoids proceeded chemoselectively and site-specifically at the N-methylaminooxy moieties. Employing microwave irradiation significantly increased the degree of glycosylation and shortened the reaction times.