Preparation of 2-amino-2-C-glycosyl-acetonitriles from C-glycosyl aldehydes by Strecker reaction

Synthesis of new 2-amino-2-C-d-glycosyl-acetonitriles in a Strecker reaction from various C-glycosyl aldehydes, chiral amines, and HCN was carried out. While aminonitriles from glycal and 2-deoxy-β-d-glycosyl aldehydes were prepared in satisfactory yields, lower yields were obtained with C-glycosyl aldehydes. Strecker reaction with the benzyl-protected 1-C-formyl-d-galactal and S- or R-1-phenylethylamine (S-PEA or R-PEA) yielded predominantly the R-configured C-glycosyl aminoacetonitrile. The direction of the nucleophilic addition appears to be governed by the configuration of the anomeric carbon with β-linked sugars. Since the stereochemistry of the transition state is unknown according to the configuration of the major product a Felkin–Ahn selectivity can be mainly presumed.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Preparation of new 2-amino-2-C-d-glycosyl-acetonitriles by Strecker reaction from protected C-glycosyl formaldehydes. ► Configuration assignment of the diastereomeric products by 1H NMR. ► Studies on stereochemical outcome as the function of the anomeric configuration. ► Double asymmetric induction by carbohydrates and chiral amines. ► Employing thiourea organocatalysts in the preparation of C-glyco-aminonitriles.