John P. Shilvock, Robert J. Nash, Alison A. Watson, Ana L. Winters, Terry D. Butters, Raymond A. Dwek, David A. Winkler and George W. J. Fleet
The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono-1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogenation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective α-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of α-galactosidases over naringinase (L-rhamnosidase) are also reported.