Linkage-Editing of Melibiosamine: Synthesis and Biological Evaluation of CH- and CHF-Linked Analogs.

Melibiosamine (Gal-α(1,6)-GlcNH), consisting of galactose and glucosamine linked by an α(1,6)-glycosidic bond, is an artificial disaccharide derivative that selectively inhibits the proliferation of K562 tumor cells relative to HUC-F2 normal cells. In this study, we employed a linkage-editing strategy to synthesize CH- and CHF-linked melibiosamine analogs through chemo- and stereoselective hydrogenation of fluorovinyl--glycoside. ()-CHF-Melibiosamine exhibited more potent antiproliferative activity than -linked melibiosamine, while ()-CHF-melibiosamine was less potent.

Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl--Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities.

The acetal (-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore -glycosides are of interest as more stable analogs. We hypothesized that, if the -glycoside linkage plays a vital role in glycan function, the biological activities of -glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans).

Synthesis of CH-linked α-galactosylceramide and its glucose analogues through glycosyl radical-mediated direct C-glycosylation.

We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH-linked analogue of antitumor-active KRN7000 and its glucose congener.

Synthesis of CH-Linked α(1,6)-Disaccharide Analogues by α-Selective Radical Coupling C-Glycosylation.

C-Linked carbohydrate structure, in which the cleavable O-glycosidic linkage is replaced by a carbon unit, is a useful tool for functional analyses of glycoconjugates. We describe a synthetic method for α-CH-linked disaccharide structures, such as Glc(1,6)-Glc, by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp hybridized xanthate donor and a carefully designed acceptor.