Synthesis of 3,4,6-Tri-O-acetyl-2-oximino-α-D-hexopyranosides

Abstract

The reaction of the dimeric nitrosyl chloride adducts of tri-O-acetyl-D-glucal and tri-O-acetyl-D-galactal with alcohols and phenols in dimethylformamide at room temperature provides the corresponding tri-O-acetyl-2-oximino-α-D-hexopyranosides in good to excellent yields. The condensation can also be carried out in tetrahydrofuran in the presence of pyridine or simply in refluxing methylene chloride for the simple alkyl alcohols. The stereospecificity of the reaction is extreme; only products of one configuration for both glycosidic linkage and the oximino group were detected. This result is rationalized on the basis of a cis-configuration for a tri-O-acetyl-2-nitroso-D-glycal intermediate in the H1 half-chair conformation. The introduction of methyl groups on the carbon of the methoxy group of methyl α-D-glucopyranosides causes a progressive deshielding of the anomeric proton. The data indicate that isopropyl α-D-glycopyranosides avoid the orientation for the aglycon which has the anomeric hydrogen projecting between the two methyl groups of the aglycon. Methyl tri-O-acetyl-6-O-(tri-O-acetyl-2-oximino-α-D-arabino-hexopyranosyl)-β-D-glucopyranoside was prepared in 70% yield to illustrate the use of the method for the preparation of an α-linked disaccharide.