Nitroalkene ring closure route to carbon-linked scaffolds for mimicking α-d-mannopyranosyl natural linkage

Controlled treatment of 3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-nitro-d-manno-hept-1-enitol with sodium methoxide in methanol was stopped by decationization at a point providing about equimolar mixture of α-d-mannopyranosyl and β-d-mannopyranosyl nitromethanes, from which the target α-anomer was isolated by chemisorption chromatography on a cation exchange resin in the Ba2+ form in a 36% yield. Direct reduction of the above mixture with ferrous hydroxide in situ to the corresponding amines, followed by the selective N-acetylation and the analogical chromatographic separation of both pertinent isomers with their stable ring structures gave N-acetyl-C-α-d-mannopyranosyl-methylamine. Alternative stopping of the initial ring forming reaction with acidified methanol at the above given product ratio initiated a subsequent Nef reaction and α-d-mannopyranosyl methanal dimethyl acetal was then chromatographically separated from its β-isomer on an anion exchange resin in the OH− form. Activations of two latter C-α-d-mannopyranosyl scaffolds by acid hydrolysis into respective reactive free amine or aldehyde forms were developed as well. Detailed reinvestigation of the classical method of preparation of d-mannosyl nitromethanes by thermal dehydration of a 1-deoxy-1-nitroalditol derived from d-mannose showed a maximum occurrence of only 18% of the required α-d-mannopyranosyl anomer.