Protecting group free synthesis of urea-linked glycoconjugates: efficient synthesis of β-urea glycosides in aqueous solution

Abstract

A method for the protecting group free synthesis of β-urea-linked glycoconjugates has been developed. The one step process, involving reactions between urea and D-glucose, N-acetyl-D-glucosamine or D-xylose in acidic aqueous solution, furnishes the corresponding β-urea glycosides in modest yields. This simple and efficient procedure is applicable to the synthesis of β-urea tethered amino acid-carbohydrate conjugates.

Leuckart–Wallach Approach to Sugar Isocyanides and Its IMCRs

“…10 Glycosyl isocyanides are known and have been sporadically used in IMCRs, 11,12 however they are rather complex to synthesize via anomeric glycosyl fluorides or bromides [13][14][15][16] mostly using CN -, from the glycosyl isothiocyanate 17 via reduction or classically and most commonly using the Ugi approach (NH 2 → NHCHO → NC) from the anomeric amine (Scheme 1). [18][19][20][21][22][23] These methods either give complex mixtures (with AgCN), use harsh conditions (boiling xylene), expensive materials, limited applications, and lengthy syntheses (4-6 steps from the sugar) based on potentially dangerous azides. To revive the field of glyco-based IMCR and in continuation of our interest in this area, we introduce here a short and convenient synthesis of glycosyl and arabinosyl isocyanides directly from the sugar via a two-step procedure involving our recently published modified Leuckart- Wallach procedure.…”