Cut-insert-stitch editing reaction (CIStER) sequence for surgical chemical glycan editing

Abstract

Post-synthetic surgical editing enables synthesizing diverse molecules from a common scaffold. Editing carbohydrates by inserting a foreign glycan is still a far-reaching goal for synthetic chemists. In this study, a one-pot-three-step chemical approach was employed to edit glycoconjugates. It is comprised of three steps: the first is a ‘cut’ step, cleaving one of the interglycosidic bonds and producing an intermediate that could be intercepted with 4-mercaptotoluene; second step activates the thiotolyl glycoside in the presence of an aglycon containing an orthogonally activatable ethynylcycloxyl carbonate moiety; and the third step involves ‘stitching’ by activating the carbonate donor. The cut-insert stitch-editing reaction (CIStER) is demonstrated by inserting branched and linear arabinans reminiscent of M. tuberculosis cell wall from the same designer trimannoside. Glycosylating an activated hydroxyacid (serinyl, steroidal, and lipid) after cutting the interglycosidic bond and stitching in the presence of base extendes the CIStER approach to the synthesis of glycohybrids.