Synthesis of 1,6-Anhydro-β-D-hexopyranoses Fused to the Piperidine Ring

Abstract

Two piperidine derivatives (6 and 17) containing fused 1,6-anhydro-β-D-hexopyranose moiety were prepared from 1,6-anhydro-β-D-glucopyranose (1). The first synthetic route led via the known 1,6:2,3-dianhydro-4-deoxy-4-(3-hydroxypropyl)-β-D-mannopyranose (2) obtained in four steps from 1. Its hydroxyl group was converted into amino group via tosylate and azide. The corresponding amino epoxide 5 readily rearranged into 3-amino-1,6-anhydro-3,4-dideoxy-3-N,4-C-(propane-1,3-diyl)-β-D-altropyranose (6). The second route used the known 1,6-anhydro-2,4-di-O-tosyl-β-D-ribo-hexopyranos-3-ulose (9) as an intermediate. Addition of allylmagnesium chloride to ketose 9 afforded 3-C-allyl-1,6-anhydro-2,4-di-O-tosyl-β-D-allopyranose (10). Hydroboration of its double bond followed by transformation of the resulting primary hydroxyl group into tosylamido group gave tritosyl derivative 15. Intramolecular replacement of the tosyloxy group in position 4 by tosylamido group gave tosylated piperidine derivative 16. Detosylation of 16 afforded the target 4-amino-1,6-anhydro-3,4-dideoxy-3-C,4-N-(propane-1,3-diyl)-β-D-gulopyranose (17).