Title : Self-promoted glycosylation for the synthesis of N-glycosyl sulfonyl amides
Abstract:
N-linked glycopeptides are naturally occurring glycosyl amides involved in various biological events e.g., processes on the cell surface. Synthesis of N-linked glycopeptides is intrinsically challenging since it requires control of stereoselectivity. Typically, in such glycoconjugates asparagine residue is attached to the suitable carbohydrate structure through the β-glycosidic linkage. Apart from glycosyl amides, glycosyl sulfonamides have emerged as another noteworthy class of glycosides due to their antitumor activity and inhibition potency toward carbonic anhydrase.
Here we demonstrate a direct, self-promoted glycosylation method for the formation of N-glycosides bearing both, the amide and the sulfonamide functions. The developed N-glycosylation is a two-component reaction, analogous to the previously reported method employing glycosyl trichloroacetimidate (TCA) donors and N-sulfonyl carbamate acceptors. In this work, N-sulfonyl amides have been investigated as another example of electron-poor acceptors. Due to the electron-withdrawing character of the sulfonyl moiety, the acceptors can activate the acid-labile TCA donors leading to glycosidic bond formation. Hence no additional catalysts, promoters, or additives have to be added. The scope of various TCA donors and sulfonamide acceptors equipped with different protective groups have been studied in a series of glycosylations. Certain trends in terms of reactivity were observed based on the obtained results. The anomeric configuration of the donor has been found to influence the stereoselective outcome. Glycosylations using α-configured TCA donors resulted in high β-selectivity. The reaction takes place in several commonly used organic solvents. Interestingly, the glycosylations carried out at benign temperatures afforded the O-glycosides predominantly. However, these derivatives easily rearranged at elevated temperatures giving the corresponding β-N-glycosides.
Audience take-away:
- The audience will learn about the novel N-glycosylation method requiring no catalysts, promoters, or scavengers. The developed glycosylation is an example of the additive-free reaction and therefore it complies with current trends in organic synthesis.
- The reaction deals with one of the major importance in the preparation of glycosides which is the control of stereoselectivity.
- The presented studies regard the synthesis of biologically relevant compounds.
